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Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor

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ClinicalTrials.gov Identifier: NCT01001221
Recruitment Status : Terminated (Maximum tolerated dose not able to be determined)
First Posted : October 26, 2009
Results First Posted : September 11, 2013
Last Update Posted : September 11, 2013
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Malignant
Interventions Drug: cabazitaxel
Drug: gemcitabine
Enrollment 19
Recruitment Details Participants were enrolled in 4 sites in the United States. Since it was not possible to determine the maximum Tolerated Dose (MTD) in study part 1, no participant was enrolled in study part 2 and the study was stopped.
Pre-assignment Details

At each dose level, there was a 1-week gap between the treatment of the first participant and the next 2 participants to evaluate toxicity.

Before escalating to the next dose level, at least 3 participants were to be evaluable for the criteria defining dose limiting toxicity (DLT).

Arm/Group Title Part 1: Cabazitaxel + Gemcitabine Dose Level 0 Part 1: Cabazitaxel + Gemcitabine Dose Level -1 Part 1: Cabazitaxel + Gemcitabine Dose Level -2 Part 1: Gemcitabine + Cabazitaxel Dose Level 0 Part 2: Cabazitaxel + Gemcitabine MTD
Hide Arm/Group Description

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Period Title: Overall Study
Started 5 5 3 6 0 [1]
Treated 5 5 2 6 0
Completed 1st Treatment Cycle 5 5 2 6 0
Completed 0 [2] 0 [2] 0 [2] 0 [2] 0
Not Completed 5 5 3 6 0
Reason Not Completed
Adverse Event             1             2             0             2             0
Disease progression             3             2             2             4             0
Not specified             1             1             0             0             0
Not treated; protocol exclusion             0             0             1             0             0
[1]
Inability to determine the MTD during study part 1
[2]
Participants treated until disease progression or unacceptable toxicity.
Arm/Group Title Part 1: Cabazitaxel + Gemcitabine Dose Level 0 Part 1: Cabazitaxel + Gemcitabine Dose Level -1 Part 1: Cabazitaxel + Gemcitabine Dose Level -2 Part 1: Gemcitabine + Cabazitaxel Dose Level 0 Total
Hide Arm/Group Description

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Total of all reporting groups
Overall Number of Baseline Participants 5 5 3 6 19
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
60.8  (6.6) 59.2  (9.2) 53.0  (14.8) 56.3  (16.1) 57.7  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
Female
2
  40.0%
2
  40.0%
1
  33.3%
3
  50.0%
8
  42.1%
Male
3
  60.0%
3
  60.0%
2
  66.7%
3
  50.0%
11
  57.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
Asian/Oriental 0 0 1 0 1
Black 0 1 0 0 1
Caucasian/White 4 4 2 6 16
Other 1 0 0 0 1
Body Surface Area  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
1.87  (0.32) 1.82  (0.21) 1.98  (0.42) 1.84  (0.12) 1.87  (0.24)
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
0 0 2 1 1 4
1 5 3 2 5 15
2 0 0 0 0 0
[1]
Measure Description:

ECOG criteria:

  • 0: Fully active
  • 1: Ambulatory, carry out work of a light or sedentary nature
  • 2: Ambulatory, capable of all selfcare
  • 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours
  • 4: Completely disabled, no selfcare, totally confined to bed or chair
  • 5: Dead
Primary Tumor Site  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
Bladder 0 0 1 1 2
Colon 0 1 0 0 1
Head/neck 0 1 1 0 2
Lung 2 1 1 0 4
Muscle/soft tissue 0 0 0 1 1
Other 0 1 0 0 1
Ovaries 0 0 0 1 1
Pancreas 1 1 0 1 3
Pelvis 0 0 0 1 1
Prostate 2 0 0 0 2
Skin 0 0 0 1 1
Histological Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
Adenocarcinoma 2 4 0 2 8
Squamous cell carcinoma 0 1 0 0 1
Other 3 0 3 4 10
Stage at Diagnosis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
Stage I 0 0 0 0 0
Stage II 0 1 0 0 1
Stage III 0 3 0 1 4
Stage IV 5 0 0 2 7
Unknown 0 1 3 3 7
[1]
Measure Description:

Cancer staging is on a scale of I-IV with higher numbers indicating an increase in progression of the disease.

Stage I: cancers are localized to one part of the body. Stage II: cancers are early locally advanced. Stage III: cancers are late locally advanced. Stage IV: cancers have often metastasized, or spread to other organs or throughout the body.

Number of Organs Involved  
Mean (Standard Deviation)
Unit of measure:  Organs
Number Analyzed 5 participants 5 participants 3 participants 6 participants 19 participants
4.0  (1.6) 2.6  (0.5) 3.3  (0.6) 2.0  (0.6) 2.9  (1.2)
1.Primary Outcome
Title Participants With Dose Limiting Toxicities During Dose Escalation
Hide Description Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).
Time Frame Day 1 to Day 21 of the first treatment cycle
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

DLT population: All participants who completed assessments for DLT evaluation for Cycle 1 and either:

  • received study treatment during Cycle 1 and had DLT or
  • did not have DLT and received a full dose of study treatment (no delay/reduction) during Cycle 1 and did not receive hematopoietic growth factors.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 2 5
Measure Type: Number
Unit of Measure: participants
2 2 2 2
2.Primary Outcome
Title Objective Response Rate With MTD
Hide Description

Objective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator.

CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm.

PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.

The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Time Frame Fron Day 1 up to a maximum of 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cabazitaxel + Gemcitabine MTD
Hide Arm/Group Description:

Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the maximum tolerated dose as determined in study part 1

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Time To Progression With MTD
Hide Description

Time to progression (TTP) was defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression (>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions).

Median TTP was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Time Frame Fron Day 1 up to a maximum of 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cabazitaxel + Gemcitabine MTD
Hide Arm/Group Description:

Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the maximum tolerated dose as determined in study part 1

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Duration of Response With MTD
Hide Description

Duration of Response (DR) was defined as the time from the first documentation of RECIST-defined objective tumor response to the first documentation of RECIST-defined objective tumor progression or death.

Median DR was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

Time Frame Fron Day 1 up to a maximum of 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cabazitaxel + Gemcitabine MTD
Hide Arm/Group Description:

Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the maximum tolerated dose as determined in study part 1

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Participants With Adverse Events
Hide Description

Summary of participants with adverse events (AEs) according to severity and relationship to study drug as assessed by the investigator. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used to grade the severity of AE.

Treatment-emergent adverse events (TEAEs) are AEs that occurred or worsened from start of treatment up to 30 days after treatment ceased.

NCI CTCAE v.3.0 grade 3 =severe and grade 4= life-threatening or disabling.

Time Frame from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 6
Measure Type: Number
Unit of Measure: participants
Any AE 5 5 2 6
Any TEAE 5 5 2 6
- Drug-related TEAE 5 5 2 6
Grade 3-4 TEAE 5 5 2 6
- Grade 3-4 drug-related TEAE 4 5 2 6
Serious TEAE 5 2 2 4
- Drug-related serious TEAE 3 2 2 3
AE leading to drug withdrawn 2 2 0 2
- Drug-related AE leading to drug withdrawn 0 2 0 1
AE leading to death 1 0 0 0
AE leading to dose reduction 3 4 2 4
AE leading to dose delay 4 2 1 4
6.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax)
Hide Description

Blood samples for cabazitaxel assay were collected during cycle 1 and cabazitaxel plasma concentrations were determined using a validated liquid chromatography with tandem mass spectometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1 ng/mL.

Pharmacokinetic (PK) parameters were calculated from plasma concentrations using non-compartmental analysis.

Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample, and with no prohibited concomitant medications
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 6
Mean (Standard Deviation)
Unit of Measure: ng/ml
123  (43.7) 150  (80.9) 273  (21.9) 118  (43.9)
7.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 6
Median (Full Range)
Unit of Measure: hours (hr)
1.00
(0.92 to 1.05)
0.94
(0.87 to 0.95)
0.94
(0.88 to 1.00)
0.93
(0.92 to 1.03)
8.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
Hide Description Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to the last measurable concentration at time t.
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 6
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
556  (500) 352  (101) 344  (114) 315  (208)
9.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC)
Hide Description Area under the plasma concentration versus time curve extrapolated to infinity
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Six participants' assays could not be used for AUC.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 3 3 2 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
876  (730) 420  (77.3) 462  (156) 306  (50.1)
10.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 6
Mean (Standard Deviation)
Unit of Measure: hours (hr)
92.1  (40.3) 88.3  (35.1) 75.6  (27.8) 70.3  (43.1)
11.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Six participants' assays could not be used for CL.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 3 3 2 3
Mean (Standard Deviation)
Unit of Measure: L/hr
61.0  (38.4) 64.3  (16.2) 59.5  (6.38) 90.8  (7.15)
12.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. One participant's assay could not be used for Vss.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 5
Mean (Standard Deviation)
Unit of Measure: L
6780  (3250) 4980  (818) 3930  (1170) 5570  (2100)
13.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Six participants' assays could not be used for CL/BSA.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 3 3 2 3
Mean (Standard Deviation)
Unit of Measure: L/hr/m^2
32.4  (18.3) 36.1  (6.58) 31.9  (12.6) 49.6  (8.56)
14.Secondary Outcome
Title Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
Hide Description [Not Specified]
Time Frame before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. One participant's assays could not be used for Vss/BSA.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 4 2 5
Mean (Standard Deviation)
Unit of Measure: L/m^2
3530  (1650) 2690  (434) 1980  (8.83) 3020  (1130)
15.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)
Hide Description

Blood samples for gemcitabine assay were collected on Day 1 of cycle 1 at the following timepoints:

  • Cabazitaxel + Gemcitabine: prior the start of cabazitaxel infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of gemcitabine infusion;
  • Gemcitabine + cabazitaxel: prior the start of gemcitabine infusion, immediately before the end of gemcitabine infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of cabazitaxel infusion;

Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 4 5 2 5
Mean (Standard Deviation)
Unit of Measure: ng/ml
14600  (6050) 35600  (27200) 11400  (3270) 19000  (9130)
16.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 4 5 2 5
Median (Full Range)
Unit of Measure: hours (hr)
0.49
(0.47 to 0.50)
0.38
(0.37 to 0.55)
0.60
(0.53 to 0.67)
0.42
(0.37 to 0.50)
17.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 4 5 2 5
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
7320  (1650) 16000  (11100) 6120  (3350) 9920  (5290)
18.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
6290  (1440) 21900  (10800) 8530 [1]   (NA) 9970  (5310)
[1]
Single participant in analysis
19.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: hours
0.295  (0.118) 0.254  (0.0570) 0.202 [1]   (NA) 0.256  (0.0933)
[1]
Single participant in analysis
20.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: L/hr
313  (120) 85.1  (40.6) 123 [1]   (NA) 174  (106)
[1]
Single participant in analysis
21.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: L
135  (86.2) 28.9  (30.4) 47.0 [1]   (NA) 51.6  (28.8)
[1]
Single participant in analysis
22.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: L/hr/m^2
159  (31.3) 49.8  (27.0) 78.4 [1]   (NA) 96.4  (62.8)
[1]
Single participant in analysis
23.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Five participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 3 1 5
Mean (Standard Deviation)
Unit of Measure: L/m^2
66.5  (31.7) 17.3  (18.9) 29.9 [1]   (NA) 28.7  (17.4)
[1]
Single participant in analysis
24.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)
Hide Description

Blood samples for gemcitabine assay were collected on Day 8 of cycle 1 at the following timepoints:

  • Cabazitaxel + Gemcitabine: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1.5, 3.5 and 22.5 hours after the end of infusion;
  • Gemcitabine + cabazitaxel: prior the start of infusion, immediately before the end of infusion, 15, 30 minutes, 1, 1.5, 2.5, 9 and 23.5 hours after the end of infusion;

Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 4 0 3
Mean (Standard Deviation)
Unit of Measure: ng/ml
10200  (283) 34500  (30800) 14100  (12200)
25.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 4 0 3
Median (Full Range)
Unit of Measure: hours (hr)
0.52
(0.52 to 0.52)
0.45
(0.42 to 0.55)
0.47
(0.40 to 0.48)
26.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 4 0 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
5530  (1150) 15300  (11900) 7710  (6840)
27.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: hours (hr)
0.222 [1]   (NA) 0.282  (0.0218) 0.317  (0.113)
[1]
Single participant in analysis
28.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
6360 [1]   (NA) 18500  (12300) 7780  (6880)
[1]
Single participant in analysis
29.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: L/hr
262 [1]   (NA) 110  (55.8) 252  (158)
[1]
Single participant in analysis
30.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: L
104 [1]   (NA) 36.2  (19.4) 93.3  (51.7)
[1]
Single participant in analysis
31.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: L/hr/m^2
157 [1]   (NA) 62.8  (32.7) 143  (93.3)
[1]
Single participant in analysis
32.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Standard Deviation)
Unit of Measure: L/m^2
62.2 [1]   (NA) 20.6  (11.6) 52.3  (28.6)
[1]
Single participant in analysis
33.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)
Hide Description

Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU).

2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 5
Mean (Standard Deviation)
Unit of Measure: ng/ml
32200  (10000) 32500  (10800) 25500  (8770) 21100  (5980)
34.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 5
Median (Full Range)
Unit of Measure: hours
0.73
(0.50 to 0.77)
0.77
(0.47 to 0.83)
0.65
(0.53 to 0.77)
0.77
(0.50 to 1.47)
35.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 5
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
227000  (27500) 235000  (47400) 167000  (47500) 168000  (57000)
36.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 5
Mean (Standard Deviation)
Unit of Measure: hours
9.07  (2.22) 9.41  (0.837) 7.96  (1.87) 12.1  (5.17)
37.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined. Two participants' assays could not be used in the analysis.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
273000  (58100) 285000  (61200) 191000  (66900) 151000  (37700)
38.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)
Hide Description

Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU).

2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL.

PK parameters were calculated from plasma concentrations using non-compartmental analysis.

Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample and with no prohibited concomitant medications.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 0 3
Mean (Standard Deviation)
Unit of Measure: ng/ml
27400  (3180) 34800  (8630) 18700  (4740)
39.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 0 3
Median (Full Range)
Unit of Measure: hours
0.69
(0.52 to 0.85)
0.68
(0.55 to 1.02)
0.72
(0.70 to 1.00)
40.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 0 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
216000  (3700) 287000  (77500) 141000  (26400)
41.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 0 3
Mean (Standard Deviation)
Unit of Measure: hours
7.29  (1.11) 8.55  (0.820) 9.10  (0.484)
42.Secondary Outcome
Title Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)
Hide Description [Not Specified]
Time Frame 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population as previously defined
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 2 5 0 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/ml
240000  (11300) 340000  (100000) 168000  (27600)
43.Secondary Outcome
Title Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC
Hide Description Ratio Day 1/Day 8 for AUClast and AUC were calculated to assess the effect of cabazitaxel on gemcitabine exposure.
Time Frame Day 1 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) and Day 8 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants who received at least 1 part of a dose of study treatment and had valid Day 1 and Day 8 PK samples. Valid PK samples included at least 1 post treatment analyzable PK sample and no prohibited concomitant medications.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 1 3 0 3
Mean (Full Range)
Unit of Measure: ratio
AUClast
1.15 [1] 
(NA to NA)
1.17
(0.661 to 2.49)
1.11
(0.994 to 1.25)
AUC
1.15 [1] 
(NA to NA)
1.24
(0.660 to 2.47)
1.11
(0.994 to 1.25)
[1]
Single participant in analysis
44.Post-Hoc Outcome
Title Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Hide Description

Participant Best response was assessed by investigator using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1:

  • Complete response (CR): Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm:
  • Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion;
  • Progressive disease (PD): >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions;
  • Stable disease (SD): not a CR, PR or PD.
Time Frame Up to a maximum of 22 cycles (median 4 cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment.
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description:

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Overall Number of Participants Analyzed 5 5 2 6
Measure Type: Number
Unit of Measure: participants
Complete response 0 0 0 0
Partial response 1 1 0 1
Stable disease 2 3 0 3
Progressive disease 1 1 2 2
Not evaluable 1 0 0 0
Time Frame from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Hide Arm/Group Description

Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8

21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision

All-Cause Mortality
Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   2/5 (40.00%)   2/2 (100.00%)   4/6 (66.67%) 
Blood and lymphatic system disorders         
Febrile neutropenia  1  1/5 (20.00%)  0/5 (0.00%)  2/2 (100.00%)  1/6 (16.67%) 
Neutropenia  1  1/5 (20.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Pancytopenia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Leukopenia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  1/6 (16.67%) 
Cardiac disorders         
Supraventricular tachycardia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders         
Intestinal dilatation  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Intestinal obstruction  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
General disorders         
Disease progression  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Chest pain  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Pyrexia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Infections and infestations         
Bronchiolitis  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Pneumonia  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Sepsis  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Investigations         
Blood electrolytes abnormal  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Aspartate aminotransferase increased  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to central nervous system  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Nervous system disorders         
Headache  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Hypoxia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cabazitaxel + Gemcitabine Dose Level 0 Cabazitaxel + Gemcitabine Dose Level -1 Cabazitaxel + Gemcitabine Dose Level -2 Gemcitabine + Cabazitaxel Dose Level 0
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   5/5 (100.00%)   2/2 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders         
Neutropenia  1  4/5 (80.00%)  3/5 (60.00%)  1/2 (50.00%)  3/6 (50.00%) 
Lymphopenia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  1/5 (20.00%)  2/5 (40.00%)  1/2 (50.00%)  3/6 (50.00%) 
Anaemia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  4/6 (66.67%) 
Leukopenia  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Normochromic normocytic anaemia  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Eye disorders         
Vision blurred  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Vitreous floaters  1  0/5 (0.00%)  2/5 (40.00%)  0/2 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  2/5 (40.00%)  4/5 (80.00%)  0/2 (0.00%)  2/6 (33.33%) 
Abdominal pain  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Abdominal pain upper  1  1/5 (20.00%)  0/5 (0.00%)  1/2 (50.00%)  1/6 (16.67%) 
Constipation  1  1/5 (20.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Nausea  1  1/5 (20.00%)  4/5 (80.00%)  0/2 (0.00%)  2/6 (33.33%) 
Abdominal distension  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Dry mouth  1  0/5 (0.00%)  1/5 (20.00%)  1/2 (50.00%)  0/6 (0.00%) 
Dyspepsia  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Flatulence  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Oral pain  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Vomiting  1  0/5 (0.00%)  2/5 (40.00%)  0/2 (0.00%)  0/6 (0.00%) 
General disorders         
Asthenia  1  2/5 (40.00%)  2/5 (40.00%)  0/2 (0.00%)  0/6 (0.00%) 
Fatigue  1  2/5 (40.00%)  4/5 (80.00%)  1/2 (50.00%)  5/6 (83.33%) 
Chest discomfort  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Chills  1  1/5 (20.00%)  1/5 (20.00%)  1/2 (50.00%)  1/6 (16.67%) 
Pain  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Catheter site haematoma  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Catheter site pain  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Early satiety  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Generalized oedema  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Injection site reaction  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Musosal inflammation  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Oedema peripheral  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  3/6 (50.00%) 
Pyrexia  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  2/6 (33.33%) 
Immune system disorders         
Drug hypersensitivity  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Infections and infestations         
Upper respiratory tract infection  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Eye infection  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Gastroenteritis viral  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Oral herpes  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Urinary tract infection  1  0/5 (0.00%)  1/5 (20.00%)  1/2 (50.00%)  0/6 (0.00%) 
Viral infection  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Viral upper respiratory tract infection  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications         
Excoriation  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Anastomotic ulcer  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Investigations         
Weight decreased  1  3/5 (60.00%)  1/5 (20.00%)  1/2 (50.00%)  1/6 (16.67%) 
Alanine aminotransferase increased  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Aspartate aminotransferase increased  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Blood alkalne phosphatase increased  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Metabolism and nutrition disorders         
Decreased appetite  1  2/5 (40.00%)  3/5 (60.00%)  0/2 (0.00%)  4/6 (66.67%) 
Dehydration  1  1/5 (20.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Hypokalaemia  1  1/5 (20.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Hypophosphataemia  1  1/5 (20.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Gout  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Hypomagnesaemia  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Musculoskeletal stiffness  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Arthalgia  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  2/6 (33.33%) 
Bone pain  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Muscle spasms  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Musculoskeletal chest pain  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Myalgia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Seborrhoeic keratosis  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Nervous system disorders         
Neuropathy peripheral  1  1/5 (20.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Paraesthesia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Balance disorder  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Dizziness  1  0/5 (0.00%)  2/5 (40.00%)  1/2 (50.00%)  0/6 (0.00%) 
Dysgeusia  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  2/6 (33.33%) 
Headache  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Memory impairment  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Somnolence  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Psychiatric disorders         
Abnormal dreams  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Depression  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Insomnia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  2/6 (33.33%) 
Reproductive system and breast disorders         
Vaginal discharge  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/5 (20.00%)  1/5 (20.00%)  1/2 (50.00%)  2/6 (33.33%) 
Dyspnoea  1  1/5 (20.00%)  0/5 (0.00%)  1/2 (50.00%)  1/6 (16.67%) 
Dyspnoea exertional  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Hypoxia  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Nasal congestion  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Productive cough  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Epistaxis  1  0/5 (0.00%)  1/5 (20.00%)  2/2 (100.00%)  0/6 (0.00%) 
Laryngeal inflammation  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Oropharyngeal pain  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Pleural effusion  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Rhinorrhoea  1  0/5 (0.00%)  0/5 (0.00%)  0/2 (0.00%)  1/6 (16.67%) 
Upper-airway cough syndrome  1  0/5 (0.00%)  0/5 (0.00%)  1/2 (50.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash  1  2/5 (40.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Hyperkeratosis  1  1/5 (20.00%)  0/5 (0.00%)  0/2 (0.00%)  0/6 (0.00%) 
Alopecia  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Night sweats  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  1/6 (16.67%) 
Pruritus  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Rash maculo-papular  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Vascular disorders         
Hypotension  1  1/5 (20.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Orthostatic hypotension  1  0/5 (0.00%)  1/5 (20.00%)  0/2 (0.00%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Pharmacokinetic results need to be confirmed due to the limited data available.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
At least 45 days in advance of proposed submission, the Investigator should forward a copy of the manuscript or abstract for review by the sponsor, and, if necessary, delay publication or communication for a limited time in order to protect the confidentiality or proprietary nature of any information contained therein.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01001221     History of Changes
Other Study ID Numbers: TCD11068
First Submitted: October 23, 2009
First Posted: October 26, 2009
Results First Submitted: May 20, 2013
Results First Posted: September 11, 2013
Last Update Posted: September 11, 2013