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Trial record 43 of 59 for:    MLN8237

Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02367352
Recruitment Status : Terminated (Sponsor's decision)
First Posted : February 20, 2015
Results First Posted : May 2, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Ovarian Cancer
Small Cell Lung Cancer
Interventions Drug: Alisertib
Drug: Paclitaxel
Enrollment 9
Recruitment Details Participants took part in the study at 3 investigative sites in Japan and Republic of Korea from 19 March 2015 to 23 May 2017.
Pre-assignment Details Participants with a diagnosis of Advanced Solid Tumors were enrolled in a dose escalation phase to receive a starting dose of alisertib 15 mg plus paclitaxel 60 mg/m^2. The dose expansion phase was not conducted.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase) Dose Expansion Cohort
Hide Arm/Group Description Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 9 0 0
Completed 0 0 0
Not Completed 9 0 0
Reason Not Completed
Progressive disease             7             0             0
Participant Received Alternative Therapy             1             0             0
Adverse Event             1             0             0
Arm/Group Title Cohort 1 (Dose Escalation Phase)
Hide Arm/Group Description Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
Safety population is defined as all participants who received at least 1 dose of alisertib. Participants were only enrolled in Dose Escalation Cohort 1.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants
57.48  (14.621)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
2
  22.2%
Male
7
  77.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Not Hispanic or Latino
7
  77.8%
Not reported
2
  22.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 9 participants
9
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants
Japan 3
Korea, Republic Of 6
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 9 participants
162.77  (6.907)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 9 participants
63.70  (10.165)
Body Surface Area  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 9 participants
1.693  (0.1542)
1.Primary Outcome
Title Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time Frame From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 9 0
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
9
 100.0%
SAEs
4
  44.4%
2.Primary Outcome
Title Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings
Hide Description The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events.
Time Frame From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 9 0
Measure Type: Count of Participants
Unit of Measure: Participants
Neutrophil Count Decreased
5
  55.6%
White Blood Cell Count Decreased
4
  44.4%
Blood Antidiuretic Hormone Abnormal
1
  11.1%
3.Primary Outcome
Title Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings
Hide Description The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events.
Time Frame From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 9 0
Measure Type: Count of Participants
Unit of Measure: Participants
1
  11.1%
4.Primary Outcome
Title Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Primary Outcome
Title Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Primary Outcome
Title Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Primary Outcome
Title Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Primary Outcome
Title Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Primary Outcome
Title Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Primary Outcome
Title Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis.
Arm/Group Title Cohort 1 (Dose Escalation Phase) Cohort 2 (Dose Escalation Phase)
Hide Arm/Group Description:
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Primary Outcome
Title Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time Frame From Day 1 to 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Primary Outcome
Title Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings
Hide Description The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.
Time Frame From Day 1 to 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Primary Outcome
Title Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings
Hide Description The number of participants with any markedly abnormal vital sign values will be collected throughout study.
Time Frame From Day 1 to 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
15.Primary Outcome
Title Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Primary Outcome
Title Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Primary Outcome
Title Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Hide Description [Not Specified]
Time Frame Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
18.Primary Outcome
Title Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
19.Primary Outcome
Title Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
20.Primary Outcome
Title Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
21.Primary Outcome
Title Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
22.Primary Outcome
Title Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
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Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Dose Expansion Phase: Overall Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months)
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Hide Analysis Population Description
The dose expansion phase was cancelled by the sponsor.
Arm/Group Title Dose Expansion Cohort
Hide Arm/Group Description:
Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were only enrolled in Dose Escalation Cohort 1.
 
Arm/Group Title Cohort 1 (Dose Escalation Phase)
Hide Arm/Group Description Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles).
All-Cause Mortality
Cohort 1 (Dose Escalation Phase)
Affected / at Risk (%)
Total   1/9 (11.11%) 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 (Dose Escalation Phase)
Affected / at Risk (%)
Total   4/9 (44.44%) 
Gastrointestinal disorders   
Diarrhoea  1  1/9 (11.11%) 
General disorders   
Disease progression  1  1/9 (11.11%) 
Infections and infestations   
Pneumonia  1  1/9 (11.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Small cell lung cancer (disease progression)  1 [1]  1/9 (11.11%) 
Nervous system disorders   
Dizziness  1  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/9 (11.11%) 
Pneumothorax  1  1/9 (11.11%) 
1
Term from vocabulary, MedDRA version: 19.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment with alisertib and is not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 (Dose Escalation Phase)
Affected / at Risk (%)
Total   9/9 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  3/9 (33.33%) 
Eye disorders   
Dry eye  1  1/9 (11.11%) 
Gastrointestinal disorders   
Diarrhoea  1  5/9 (55.56%) 
Stomatitis  1  4/9 (44.44%) 
Vomiting  1  4/9 (44.44%) 
Constipation  1  3/9 (33.33%) 
Abdominal pain  1  2/9 (22.22%) 
Dyspepsia  1  2/9 (22.22%) 
Nausea  1  2/9 (22.22%) 
Intestinal perforation  1  1/9 (11.11%) 
General disorders   
Fatigue  1  5/9 (55.56%) 
Asthenia  1  2/9 (22.22%) 
Chest pain  1  1/9 (11.11%) 
Chills  1  1/9 (11.11%) 
Influenza like illness  1  1/9 (11.11%) 
Malaise  1  1/9 (11.11%) 
Pyrexia  1  1/9 (11.11%) 
Infections and infestations   
Bronchitis  1  1/9 (11.11%) 
Pharyngitis  1  1/9 (11.11%) 
Upper respiratory tract infection  1  1/9 (11.11%) 
Investigations   
Neutrophil count decreased  1  5/9 (55.56%) 
White blood cell count decreased  1  4/9 (44.44%) 
Blood antidiuretic hormone abnormal  1  1/9 (11.11%) 
Metabolism and nutrition disorders   
Hyperglycaemia  1  3/9 (33.33%) 
Hyponatraemia  1  3/9 (33.33%) 
Decreased appetite  1  2/9 (22.22%) 
Hypophosphataemia  1  2/9 (22.22%) 
Hyperkalaemia  1  1/9 (11.11%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  2/9 (22.22%) 
Arthralgia  1  1/9 (11.11%) 
Flank pain  1  1/9 (11.11%) 
Myalgia  1  1/9 (11.11%) 
Nervous system disorders   
Neuropathy peripheral  1  3/9 (33.33%) 
Dizziness  1  1/9 (11.11%) 
Dysgeusia  1  1/9 (11.11%) 
Headache  1  1/9 (11.11%) 
Paraesthesia  1  1/9 (11.11%) 
Peripheral sensory neuropathy  1  1/9 (11.11%) 
Psychiatric disorders   
Delirium  1  1/9 (11.11%) 
Depression  1  1/9 (11.11%) 
Renal and urinary disorders   
Urinary retention  1  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  2/9 (22.22%) 
Oropharyngeal pain  1  1/9 (11.11%) 
Productive cough  1  1/9 (11.11%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  4/9 (44.44%) 
Rash  1  3/9 (33.33%) 
Dermatitis acneiform  1  1/9 (11.11%) 
Pruritus  1  1/9 (11.11%) 
Rash maculo-papular  1  1/9 (11.11%) 
Vascular disorders   
Superior vena cava syndrome  1  1/9 (11.11%) 
1
Term from vocabulary, MedDRA version: 19.0
Indicates events were collected by systematic assessment
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.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02367352     History of Changes
Other Study ID Numbers: C14022
U1111-1164-7696 ( Registry Identifier: WHO )
JapicCTI-152845 ( Registry Identifier: JapicCTI )
First Submitted: February 11, 2015
First Posted: February 20, 2015
Results First Submitted: April 30, 2018
Results First Posted: May 2, 2019
Last Update Posted: June 26, 2019