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Trial record 23 of 201 for:    Ovarian Dysgenesis 1

Alisertib (MLN8237) in Participants With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer

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ClinicalTrials.gov Identifier: NCT01091428
Recruitment Status : Completed
First Posted : March 24, 2010
Results First Posted : June 4, 2018
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Ovarian Carcinoma
Fallopian Tube Cancer
Peritoneal Cancer
Breast Carcinoma
Interventions Drug: Alisertib
Drug: Paclitaxel
Enrollment 191
Recruitment Details Participants took part in the study at 33 investigative sites in France, Poland and the United States from 16 April 2010 to 19 July 2017. Data cutoff for the primary analysis was 12 August 2014.
Pre-assignment Details Participants with a diagnosis of ovarian cancer or breast cancer were enrolled equally in a dose escalation study to determine the recommended Phase 2 dose. In Phase 2 participants were randomized equally to receive alisertib 40 mg BID + paclitaxel 60 mg/m^2 or single agent paclitaxel 80 mg/m^2.
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Period Title: Phase 1
Started 38 11 0 0
Completed 0 [1] 0 0 0
Not Completed 38 11 0 0
Reason Not Completed
Progressive Disease             24             8             0             0
Symptomatic Deterioration             3             2             0             0
Adverse Event             2             0             0             0
Withdrawal by Subject             7             0             0             0
Reason not specified             0             1             0             0
Single-Patient IND             2             0             0             0
[1]
Completed = participants who completed the treatment.
Period Title: Phase 2
Started 0 0 73 69
Completed 0 0 0 0
Not Completed 0 0 73 69
Reason Not Completed
Progressive Disease             0             0             44             46
Symptomatic Deterioration             0             0             1             6
Adverse Event             0             0             12             5
Withdrawal by Subject             0             0             9             8
Unsatisfactory Therapeutic Response             0             0             1             1
Reason not specified             0             0             4             3
Physician Decision             0             0             2             0
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2) Total
Hide Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Total of all reporting groups
Overall Number of Baseline Participants 38 11 73 69 191
Hide Baseline Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
55.8  (10.29) 58.6  (10.06) 61.0  (11.60) 60.8  (8.41) 59.8  (10.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
Female
38
 100.0%
11
 100.0%
73
 100.0%
69
 100.0%
191
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
4 0 1 4 9
Not Hispanic or Latino Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
34 10 64 62 170
Not Reported Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 1 7 3 11
Missing Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 1 0 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
34 11 66 55 166
Black or African American Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
3 0 2 6 11
Asian Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
1 0 1 2 4
American Indian or Alaskan Native Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 0 2 2
Other Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 1 1 2
Not Reported Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 2 3 5
Missing Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
38 11 48 45 142
Poland Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 10 8 18
France Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
0 0 15 16 31
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 38 participants 11 participants 72 participants 69 participants 190 participants
164.2  (6.41) 164.5  (6.38) 162.4  (7.02) 161.9  (7.30) 162.7  (6.99)
[1]
Measure Analysis Population Description: Height data was only available for 72 participants in the Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 arm in Phase 2.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 38 participants 11 participants 73 participants 69 participants 191 participants
75.86  (16.41) 76.29  (7.29) 70.42  (14.78) 72.50  (18.71) 72.59  (16.37)
Body Surface Area   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 38 participants 11 participants 72 participants 69 participants 190 participants
1.850  (0.21) 1.865  (0.10) 1.776  (0.20) 1.794  (0.24) 1.802  (0.21)
[1]
Measure Description: Body Surface Area (m^2) = square root [height (cm) x weight (kg) / 3600].
[2]
Measure Analysis Population Description: Body Surface Area was only calculated for 72 participants in the Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 arm in Phase 2.
1.Primary Outcome
Title Phase 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) for Alisertib in Combination With Paclitaxel
Time Frame Cycle 1 (Up to 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT-Evaluable Population was defined as all participants in the phase 1 who either experienced DLT during Cycle 1 or completed treatment with at least 15 of the planned 18 doses of alisertib and 2 of the planned 3 doses of paclitaxel in Cycle 1 and had sufficient follow-up data.
Arm/Group Title Alisertib + Paclitaxel (Phase 1)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: mg
40
2.Primary Outcome
Title Phase 1: MTD and RP2D for Paclitaxel in Combination With Alisertib
Hide Description The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of cycle 1).
Time Frame Cycle 1 (Up to 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT-Evaluable Population was defined as all participants in the phase 1 who either experienced DLT during Cycle 1 or completed treatment with at least 15 of the planned 18 doses of alisertib and 2 of the planned 3 doses of paclitaxel in Cycle 1 and had sufficient follow-up data.
Arm/Group Title Alisertib + Paclitaxel
Hide Arm/Group Description:
Paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: mg/m^2
60
3.Primary Outcome
Title Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious 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 First dose to 30 days past last dose (Up to 36 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 38 11
Measure Type: Number
Unit of Measure: participants
AEs 38 11
SAEs 13 2
4.Primary Outcome
Title Phase 1: Number of Participants With Clinically Significant Laboratory Values
Hide Description Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Time Frame First dose to 30 days past last dose (Up to 36 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 38 11
Measure Type: Number
Unit of Measure: participants
Neutrophil count decreased 3 0
White blood cell count decreased 1 1
Aspartate aminotransferase increased 3 1
Alanine aminotransferase increased 2 0
Ammonia increased 1 0
Transaminases increased 1 0
Blood alkaline phosphatase increased 1 1
High density lipoprotein decreased 1 0
Urine output decreased 1 0
Granulocyte count decreased 0 1
5.Primary Outcome
Title Phase 1: Number of Participants With Clinically Significant Vital Sign Findings
Hide Description Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
Time Frame First dose to 30 days past last dose (Up to 36 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 38 11
Measure Type: Number
Unit of Measure: participants
Pyrexia 8 5
Heart rate irregular 1 0
Blood pressure increased 0 1
Weight decreased 3 0
6.Primary Outcome
Title Phase 1: Number of Participants With Hypersensitivity and Neurotoxicity
Hide Description [Not Specified]
Time Frame Baseline up to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Safety population was defined as all participants who received at least 1 dose of any study drug.

Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 38 11
Measure Type: Number
Unit of Measure: participants
Hypersensitivity 1 0
Neurotoxicity 0 0
7.Primary Outcome
Title Phase 2: Progression-Free Survival (PFS)
Hide Description PFS is defined as the time from the date randomization for Phase 2 participants to the date of first documented progressive disease (PD) or death as assessed by the investigator using both RECIST 1.1 criteria and CA-125 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.
Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that has not progressed and has not died or has started the alternate therapy, PFS is censored at the last response assessment that is stable disease (SD) or better.
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Median (80% Confidence Interval)
Unit of Measure: days
204
(175 to 230)
142
(117 to 148)
8.Secondary Outcome
Title Phase 1: Combined Best Overall Response Rate (ORR) in Participants With Recurrent Ovarian Cancer or Breast Cancer
Hide Description Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)
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Hide Analysis Population Description
Response evaluable population was defined as all participants who were randomized and had measurable disease according to RECIST or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment as per either RECIST or CA-125 criteria.
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 38 11
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
47
(36 to 59)
55
(32 to 76)
9.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib in Phase 1
Hide Description [Not Specified]
Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle1 (Day1) 428.7  (189.59) 766.8  (312.10) 900.00  (392.17) 1365.3  (466.51) 1398.7  (607.70) 1960.0  (515.65)
Cycle1 (Day3) 594.3  (228.46) 1042.3  (280.95) 871.3  (268.23) 1708.5  (820.54) 2493.4  (955.31) 4456.7  (947.33)
10.Secondary Outcome
Title Tmax: Time to First Occurrence of Cmax for Alisertib in Phase 1
Hide Description [Not Specified]
Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Median (Full Range)
Unit of Measure: hour
Cycle 1, Day 1
3.0
(1 to 5)
3.1
(2 to 4)
2.6
(2 to 3)
2.5
(2 to 9)
3.0
(2 to 9)
2.0
(2 to 9)
Cycle 1, Day 3
2.2
(0 to 5)
3.0
(1 to 3)
3.5
(2 to 5)
2.0
(1 to 4)
2.0
(1 to 9)
2.0
(2 to 3)
11.Secondary Outcome
Title AUC(Tau): Area Under the Concentration-Time Curve During a Dosing Interval for Alisertib in Phase 1
Hide Description [Not Specified]
Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hour(hr)
Cycle 1, Day 1 2519.3  (937.52) 5175.0  (1766.11) 5610.0  (2105.42) 8581.7  (3225.64) 9594.0  (4600.42) 14666.7  (3707.20)
Cycle 1, Day3 3966.7  (1112.11) 7745.0  (2233.91) 6155.0  (1737.69) 12478.3  (6013.93) 17557.3  (7856.30) 35500.0  (12842.12)
12.Secondary Outcome
Title AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Phase 1
Hide Description [Not Specified]
Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1 2519.3  (937.52) 5175.0  (1766.11) 5610.0  (2105.42) 8581.7  (3225.64) 9594.0  (4600.42) 14666.7  (3707.20)
Cycle 1, Day 3 3966.7  (1112.11) 7745.0  (2233.91) 6155.0  (1737.69) 12478.3  (6013.93) 17557.3  (7856.30) 35500.0  (12842.12)
13.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1, Day 1 Number Analyzed 15 participants 6 participants 4 participants 5 participants 15 participants 3 participants
3097.3  (1114.51) 3120.0  (447.75) 2117.5  (745.54) 2448.0  (988.65) 1917.3  (528.32) 1338.7  (617.94)
Cycle 2, Day 1 Number Analyzed 13 participants 6 participants 3 participants 6 participants 13 participants 2 participants
2654.6  (696.45) 3231.7  (615.64) 1733.3  (541.97) 2478.3  (878.39) 1492.7  (558.14) 1750.0  (183.85)
14.Secondary Outcome
Title AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1 Number Analyzed 13 participants 6 participants 4 participants 5 participants 15 participants 3 participants
4437.7  (1053.87) 4825.0  (735.17) 3355.0  (865.89) 3366.0  (1139.25) 2652.7  (651.32) 2190.0  (387.43)
Cycle 2, Day 1 Number Analyzed 12 participants 6 participants 3 participants 5 participants 13 participants 2 participants
4061.7  (1298.86) 5301.7  (1183.31) 2660.0  (307.90) 3056.0  (812.67) 2231.5  (604.76) 2460.0  (14.14)
15.Secondary Outcome
Title AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1 Number Analyzed 9 participants 5 participants 3 participants 4 participants 11 participants 2 participants
5317.8  (1052.40) 5238.0  (812.26) 3860.0  (824.20) 3375.0  (1130.56) 3175.5  (933.10) 2535.0  (657.61)
Cycle 2, Day 1 Number Analyzed 11 participants 5 participants 2 participants 4 participants 10 participants 0 participants
4606.4  (1391.35) 5584.0  (1367.51) 3185.0  (176.78) 3415.0  (1010.82) 2680.0  (607.22)
16.Secondary Outcome
Title t½: Terminal Half-Life for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: hour
Cycle 1, Day 1 Number Analyzed 11 participants 5 participants 3 participants 5 participants 11 participants 2 participants
17.2  (4.20) 17.5  (1.87) 17.3  (4.16) 13.9  (4.68) 16.8  (6.83) 18.4  (8.70)
Cycle 2, Day 1 Number Analyzed 12 participants 5 participants 2 participants 4 participants 10 participants 2 participants
17.0  (3.63) 16.2  (5.05) 17.3  (5.23) 16.5  (4.32) 13.3  (5.59) 14.6  (2.19)
17.Secondary Outcome
Title CL: Total Clearance After Intravenous Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: liter per hour
Cycle 1, Day 1 Number Analyzed 9 participants 5 participants 3 participants 4 participants 11 participants 2 participants
29.756  (6.8175) 28.220  (5.1804) 26.800  (7.5386) 40.950  (17.5268) 38.055  (13.7095) 38.950  (11.2430)
Cycle 2, Day 1 Number Analyzed 11 participants 5 participants 2 participants 4 participants 10 participants 0 participants
35.827  (10.4005) 28.240  (7.3748) 33.900  (5.2326) 34.250  (8.2614) 42.440  (10.4296)
18.Secondary Outcome
Title Vss: Volume of Distribution at Steady State for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: liter
Cycle 1, Day 1 Number Analyzed 9 participants 5 participants 3 participants 4 participants 11 participants 2 participants
313.444  (118.6593) 310.800  (86.9235) 330.000  (208.8851) 357.000  (158.1834) 433.909  (179.7757) 460.500  (103.9447)
Cycle 2, Day 1 Number Analyzed 11 participants 5 participants 2 participants 4 participants 10 participants 0 participants
391.364  (64.3137) 283.200  (121.1123) 413.500  (242.5376) 377.000  (118.9650) 372.600  (180.7332)
19.Secondary Outcome
Title Vz: Volume of Distribution During the Terminal Disposition Phase for Paclitaxel in Phase 1
Hide Description [Not Specified]
Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
Hide Arm/Group Description:
Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
Overall Number of Participants Analyzed 15 6 4 6 15 3
Mean (Standard Deviation)
Unit of Measure: liter
Cycle 1, Day 1 Number Analyzed 9 participants 5 participants 3 participants 4 participants 11 participants 2 participants
705.000  (179.0223) 721.600  (203.8021) 694.000  (352.1534) 850.500  (291.0401) 872.727  (328.6202) 956.500  (188.7975)
Cycle 2, Day 1 Number Analyzed 11 participants 5 participants 2 participants 4 participants 10 participants 0 participants
829.364  (156.6060) 663.200  (321.3070) 865.500  (388.2016) 777.250  (103.7027) 733.000  (208.4898)
20.Secondary Outcome
Title Phase 2: Combined Best Overall Response Rate (ORR)
Hide Description Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable population was defined as all participants who were randomized and had measurable disease according to RECIST or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment as per either RECIST or CA-125 criteria.
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 67 64
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
60
(51 to 68)
52
(43 to 60)
21.Secondary Outcome
Title Phase 2: Duration of Response (DOR)
Hide Description DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD or the last response assessment that is stable disease (SD) or better for a participant who started alternate therapy without progression. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. A responder that did not experience disease progression is censored at the last response assessment that is SD.
Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Response evaluable population, all participants who were randomized and had measurable disease according to RECIST 1.1 or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment per RECIST 1.1 or CA-125 criteria, who were responders.
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 40 33
Median (80% Confidence Interval)
Unit of Measure: days
201
(181 to 218)
169
(120 to 231)
22.Secondary Outcome
Title Phase 2: Time to Disease Progression (TTP)
Hide Description TTP was defined as the time from the date of randomization to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.
Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)
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Hide Analysis Population Description
mITT Population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that has not progressed, TTP is censored at the last response assessment that is SD or better
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Median (80% Confidence Interval)
Unit of Measure: days
204
(175 to 232)
142
(117 to 161)
23.Secondary Outcome
Title Phase 2: Overall Survival (OS)
Hide Description OS was defined as the time form the date of the randomization to the date of death.
Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)
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Hide Analysis Population Description
mITT Population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that is alive, OS will be censored at the last known date.
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Median (80% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median, upper and lower limits of CI were not reached due to low number of participants with events.
24.Secondary Outcome
Title Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious 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 First dose to 30 days past last dose (Up to 27 Months)
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Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Measure Type: Number
Unit of Measure: participants
AEs 73 66
SAEs 30 19
25.Secondary Outcome
Title Phase 2: Number of Participants With Clinically Significant Laboratory Values
Hide Description Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Time Frame First dose to 30 days past last dose (Up to 27 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Measure Type: Number
Unit of Measure: participants
Neutrophil count decreased 14 4
White blood cell count decreased 6 1
Lymphocyte count decreased 1 1
Aspartate aminotransferase increased 1 3
Alanine aminotransferase increased 1 4
Gamma-glutamyltransferase increased 0 1
Blood alkaline phosphatase increased 2 2
Haemoglobin decreased 3 1
Blood magnesium decreased 0 3
Blood creatinine increased 1 2
Platelet count decreased 2 0
International normalised ratio increased 1 0
Blood albumin decreased 1 0
Troponin T increased 0 1
26.Secondary Outcome
Title Phase 2: Number of Participants With Clinically Significant Vital Sign Findings
Hide Description Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
Time Frame First dose to 30 days past last dose (Up to 27 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description:
Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
Overall Number of Participants Analyzed 73 69
Measure Type: Number
Unit of Measure: participants
Pyrexia 15 8
Heart rate increased 1 0
Blood pressure increased 1 0
Weight decreased 8 2
27.Other Pre-specified Outcome
Title Banked Tumor Specimens for Candidate Markers of Response to Alisertib and Taxanes
Hide Description [Not Specified]
Time Frame Up to 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was originally registered as a Secondary but this Outcome Measure was Exploratory and no data was collected.
Arm/Group Title Alisertib + Paclitaxel (Phase 1)
Hide Arm/Group Description:
Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Phase 1: First dose to 30 days past last dose (Up to 36 Months); Phase 2: First dose to 30 days past last dose (Up to 27 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.
 
Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Hide Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
All-Cause Mortality
Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/38 (34.21%)      2/11 (18.18%)      30/73 (41.10%)      19/69 (27.54%)    
Blood and lymphatic system disorders         
Febrile neutropenia  1  6/38 (15.79%)  9 0/11 (0.00%)  0 9/73 (12.33%)  9 0/69 (0.00%)  0
Neutropenia  1  0/38 (0.00%)  0 0/11 (0.00%)  0 6/73 (8.22%)  7 0/69 (0.00%)  0
Anaemia  1  1/38 (2.63%)  1 0/11 (0.00%)  0 2/73 (2.74%)  4 1/69 (1.45%)  1
Haemorrhagic anaemia  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Ear and labyrinth disorders         
Hearing impaired  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Gastrointestinal disorders         
Nausea  1  1/38 (2.63%)  1 0/11 (0.00%)  0 3/73 (4.11%)  3 2/69 (2.90%)  2
Vomiting  1  1/38 (2.63%)  1 0/11 (0.00%)  0 2/73 (2.74%)  4 2/69 (2.90%)  2
Intestinal obstruction  1  0/38 (0.00%)  0 0/11 (0.00%)  0 4/73 (5.48%)  4 1/69 (1.45%)  2
Ileus  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Abdominal pain  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Abdominal pain lower  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Diarrhoea  1  1/38 (2.63%)  1 0/11 (0.00%)  0 2/73 (2.74%)  2 1/69 (1.45%)  1
Small intestinal obstruction  1 [1]  0/38 (0.00%)  0 0/11 (0.00%)  0 2/73 (2.74%)  3 2/69 (2.90%)  2
Constipation  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Stomatitis  1  0/38 (0.00%)  0 0/11 (0.00%)  0 2/73 (2.74%)  2 0/69 (0.00%)  0
Abdominal hernia obstructive  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Proctalgia  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Gastric perforation  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Intestinal perforation  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Lower gastrointestinal haemorrhage  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Ascites  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Haemorrhagic ascites  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
General disorders         
Pyrexia  1  0/38 (0.00%)  0 1/11 (9.09%)  1 3/73 (4.11%)  3 2/69 (2.90%)  2
Asthenia  1  1/38 (2.63%)  1 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Fatigue  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 1/69 (1.45%)  1
Oedema peripheral  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Hepatobiliary disorders         
Hepatic failure  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Infections and infestations         
Device related infection  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Abscess soft tissue  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  2 0/69 (0.00%)  0
Infection  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Pneumonia  1  0/38 (0.00%)  0 0/11 (0.00%)  0 3/73 (4.11%)  3 0/69 (0.00%)  0
Bronchitis  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Urinary tract infection  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Pyelonephritis  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Cellulitis  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Catheter site cellulitis  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Sepsis  1 [2]  0/38 (0.00%)  0 1/11 (9.09%)  1 1/73 (1.37%)  1 1/69 (1.45%)  1
Gastroenteritis  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Clostridium difficile infection  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Injury, poisoning and procedural complications         
Vascular access complication  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Fall  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Pubis fracture  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Investigations         
Neutrophil count decreased  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
White blood cell count decreased  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Troponin T increased  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Metabolism and nutrition disorders         
Dehydration  1  0/38 (0.00%)  0 0/11 (0.00%)  0 4/73 (5.48%)  4 0/69 (0.00%)  0
Hyponatraemia  1  1/38 (2.63%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Flank pain  1  1/38 (2.63%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Malignant pleural effusion  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Nervous system disorders         
Cerebrovascular accident  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Syncope  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Psychiatric disorders         
Confusional state  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Renal and urinary disorders         
Acute kidney injury  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Postrenal failure  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Renal failure  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism  1  0/38 (0.00%)  0 1/11 (9.09%)  1 2/73 (2.74%)  2 1/69 (1.45%)  1
Tachypnoea  1  1/38 (2.63%)  1 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Pulmonary alveolar haemorrhage  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Pleural effusion  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Skin and subcutaneous tissue disorders         
Paraneoplastic dermatomyositis  1  0/38 (0.00%)  0 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Vascular disorders         
Deep vein thrombosis  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Venous thrombosis limb  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Hypotension  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Embolism  1  0/38 (0.00%)  0 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
[1]
One treatment-emergent death occurred during treatment with alisertib and paclitaxel and was not related.
[2]
One treatment-emergent death occurred during treatment with paclitaxel and was not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/38 (100.00%)      11/11 (100.00%)      73/73 (100.00%)      64/69 (92.75%)    
Blood and lymphatic system disorders         
Neutropenia  1  24/38 (63.16%)  100 10/11 (90.91%)  58 52/73 (71.23%)  179 10/69 (14.49%)  17
Anaemia  1  22/38 (57.89%)  37 7/11 (63.64%)  13 33/73 (45.21%)  61 20/69 (28.99%)  36
Leukopenia  1  20/38 (52.63%)  47 8/11 (72.73%)  32 11/73 (15.07%)  27 3/69 (4.35%)  6
Thrombocytopenia  1  0/38 (0.00%)  0 2/11 (18.18%)  17 4/73 (5.48%)  7 1/69 (1.45%)  2
Granulocytopenia  1  3/38 (7.89%)  4 1/11 (9.09%)  4 0/73 (0.00%)  0 1/69 (1.45%)  1
Febrile neutropenia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Cardiac disorders         
Tachycardia  1  5/38 (13.16%)  5 1/11 (9.09%)  1 1/73 (1.37%)  1 2/69 (2.90%)  2
Palpitations  1  3/38 (7.89%)  5 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Ear and labyrinth disorders         
Ear pain  1  3/38 (7.89%)  4 0/11 (0.00%)  0 3/73 (4.11%)  3 1/69 (1.45%)  1
Ear congestion  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 1/69 (1.45%)  1
Endocrine disorders         
Hypothyroidism  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Eye disorders         
Dry eye  1  4/38 (10.53%)  5 2/11 (18.18%)  2 1/73 (1.37%)  1 1/69 (1.45%)  1
Lacrimation increased  1  2/38 (5.26%)  2 2/11 (18.18%)  2 2/73 (2.74%)  2 1/69 (1.45%)  1
Visual impairment  1  3/38 (7.89%)  3 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Cataract  1  1/38 (2.63%)  1 1/11 (9.09%)  1 2/73 (2.74%)  2 0/69 (0.00%)  0
Eye pruritus  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Vision blurred  1  2/38 (5.26%)  4 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Vitreous floaters  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Conjunctivitis allergic  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Meibomian gland dysfunction  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Gastrointestinal disorders         
Diarrhoea  1  27/38 (71.05%)  49 8/11 (72.73%)  11 46/73 (63.01%)  96 15/69 (21.74%)  19
Nausea  1  23/38 (60.53%)  33 5/11 (45.45%)  6 32/73 (43.84%)  54 32/69 (46.38%)  46
Stomatitis  1  15/38 (39.47%)  32 8/11 (72.73%)  10 46/73 (63.01%)  91 6/69 (8.70%)  8
Constipation  1  15/38 (39.47%)  22 3/11 (27.27%)  4 26/73 (35.62%)  33 17/69 (24.64%)  23
Abdominal pain  1  12/38 (31.58%)  19 3/11 (27.27%)  3 21/73 (28.77%)  39 20/69 (28.99%)  26
Vomiting  1  13/38 (34.21%)  42 4/11 (36.36%)  4 20/73 (27.40%)  31 18/69 (26.09%)  25
Abdominal pain upper  1  3/38 (7.89%)  5 1/11 (9.09%)  1 11/73 (15.07%)  12 4/69 (5.80%)  6
Dyspepsia  1  5/38 (13.16%)  5 1/11 (9.09%)  1 9/73 (12.33%)  12 3/69 (4.35%)  3
Abdominal distension  1  2/38 (5.26%)  2 2/11 (18.18%)  2 9/73 (12.33%)  10 4/69 (5.80%)  4
Ascites  1  3/38 (7.89%)  3 1/11 (9.09%)  1 8/73 (10.96%)  11 5/69 (7.25%)  7
Haemorrhoids  1  4/38 (10.53%)  4 0/11 (0.00%)  0 9/73 (12.33%)  10 2/69 (2.90%)  4
Gastrooesophageal reflux disease  1  4/38 (10.53%)  4 0/11 (0.00%)  0 6/73 (8.22%)  7 4/69 (5.80%)  5
Oral pain  1  5/38 (13.16%)  6 0/11 (0.00%)  0 6/73 (8.22%)  6 0/69 (0.00%)  0
Dry mouth  1  3/38 (7.89%)  3 2/11 (18.18%)  2 1/73 (1.37%)  1 3/69 (4.35%)  3
Abdominal discomfort  1  5/38 (13.16%)  6 2/11 (18.18%)  2 1/73 (1.37%)  1 0/69 (0.00%)  0
Flatulence  1  6/38 (15.79%)  9 1/11 (9.09%)  3 1/73 (1.37%)  1 0/69 (0.00%)  0
Aphthous stomatitis  1  0/38 (0.00%)  0 0/11 (0.00%)  0 5/73 (6.85%)  9 2/69 (2.90%)  2
Dysphagia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 4/73 (5.48%)  6 1/69 (1.45%)  2
Toothache  1  2/38 (5.26%)  2 0/11 (0.00%)  0 2/73 (2.74%)  2 2/69 (2.90%)  4
Rectal haemorrhage  1  2/38 (5.26%)  2 0/11 (0.00%)  0 2/73 (2.74%)  2 0/69 (0.00%)  0
Abdominal pain lower  1  2/38 (5.26%)  4 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  1
Tongue ulceration  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  2 0/69 (0.00%)  0
General disorders         
Fatigue  1  26/38 (68.42%)  29 8/11 (72.73%)  10 43/73 (58.90%)  82 31/69 (44.93%)  37
Oedema peripheral  1  15/38 (39.47%)  24 3/11 (27.27%)  3 12/73 (16.44%)  15 18/69 (26.09%)  25
Pyrexia  1  8/38 (21.05%)  11 4/11 (36.36%)  7 13/73 (17.81%)  18 7/69 (10.14%)  10
Asthenia  1  5/38 (13.16%)  6 2/11 (18.18%)  2 10/73 (13.70%)  20 8/69 (11.59%)  11
Chills  1  10/38 (26.32%)  12 0/11 (0.00%)  0 6/73 (8.22%)  6 0/69 (0.00%)  0
Non-cardiac chest pain  1  2/38 (5.26%)  2 2/11 (18.18%)  2 3/73 (4.11%)  4 0/69 (0.00%)  0
Catheter site pain  1  3/38 (7.89%)  5 0/11 (0.00%)  0 2/73 (2.74%)  2 1/69 (1.45%)  1
Peripheral swelling  1  2/38 (5.26%)  3 0/11 (0.00%)  0 2/73 (2.74%)  4 1/69 (1.45%)  1
Pain  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Chest discomfort  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Early satiety  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Localised oedema  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Immune system disorders         
Seasonal allergy  1  3/38 (7.89%)  3 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Infections and infestations         
Urinary tract infection  1  11/38 (28.95%)  29 4/11 (36.36%)  8 11/73 (15.07%)  20 4/69 (5.80%)  7
Upper respiratory tract infection  1  11/38 (28.95%)  24 4/11 (36.36%)  4 3/73 (4.11%)  4 4/69 (5.80%)  5
Sinusitis  1  3/38 (7.89%)  10 3/11 (27.27%)  3 1/73 (1.37%)  1 2/69 (2.90%)  2
Oral candidiasis  1  4/38 (10.53%)  4 0/11 (0.00%)  0 2/73 (2.74%)  2 1/69 (1.45%)  1
Oral herpes  1  2/38 (5.26%)  4 0/11 (0.00%)  0 2/73 (2.74%)  2 2/69 (2.90%)  2
Bronchitis  1  2/38 (5.26%)  2 0/11 (0.00%)  0 3/73 (4.11%)  3 0/69 (0.00%)  0
Folliculitis  1  5/38 (13.16%)  5 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Candida infection  1  0/38 (0.00%)  0 0/11 (0.00%)  0 4/73 (5.48%)  6 0/69 (0.00%)  0
Cellulitis  1  2/38 (5.26%)  5 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Influenza  1  0/38 (0.00%)  0 1/11 (9.09%)  1 2/73 (2.74%)  2 1/69 (1.45%)  1
Localised infection  1  3/38 (7.89%)  3 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Pneumonia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Viral upper respiratory tract infection  1  1/38 (2.63%)  1 1/11 (9.09%)  2 0/73 (0.00%)  0 0/69 (0.00%)  0
Catheter site cellulitis  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Skin candida  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Injury, poisoning and procedural complications         
Fall  1  8/38 (21.05%)  14 0/11 (0.00%)  0 1/73 (1.37%)  1 3/69 (4.35%)  3
Limb injury  1  2/38 (5.26%)  2 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Skin abrasion  1  3/38 (7.89%)  3 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Fibula fracture  1  0/38 (0.00%)  0 1/11 (9.09%)  2 0/73 (0.00%)  0 0/69 (0.00%)  0
Procedural pain  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Investigations         
Neutrophil count decreased  1  3/38 (7.89%)  4 0/11 (0.00%)  0 13/73 (17.81%)  22 4/69 (5.80%)  5
Weight decreased  1  3/38 (7.89%)  3 0/11 (0.00%)  0 8/73 (10.96%)  11 2/69 (2.90%)  2
White blood cell count decreased  1  1/38 (2.63%)  2 1/11 (9.09%)  6 6/73 (8.22%)  14 1/69 (1.45%)  1
Aspartate aminotransferase increased  1  3/38 (7.89%)  3 1/11 (9.09%)  2 1/73 (1.37%)  2 3/69 (4.35%)  4
Alanine aminotransferase increased  1  2/38 (5.26%)  3 0/11 (0.00%)  0 1/73 (1.37%)  2 4/69 (5.80%)  4
Blood alkaline phosphatase increased  1  1/38 (2.63%)  1 1/11 (9.09%)  2 2/73 (2.74%)  3 2/69 (2.90%)  3
Blood pressure increased  1  0/38 (0.00%)  0 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Cardiac murmur  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Granulocyte count decreased  1  0/38 (0.00%)  0 1/11 (9.09%)  2 0/73 (0.00%)  0 0/69 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite  1  12/38 (31.58%)  17 2/11 (18.18%)  2 15/73 (20.55%)  18 8/69 (11.59%)  11
Hypokalaemia  1  6/38 (15.79%)  8 4/11 (36.36%)  5 13/73 (17.81%)  27 4/69 (5.80%)  5
Hypomagnesaemia  1  8/38 (21.05%)  16 3/11 (27.27%)  3 8/73 (10.96%)  9 7/69 (10.14%)  8
Dehydration  1  7/38 (18.42%)  8 0/11 (0.00%)  0 8/73 (10.96%)  9 3/69 (4.35%)  4
Hyperglycaemia  1  2/38 (5.26%)  3 1/11 (9.09%)  3 2/73 (2.74%)  2 2/69 (2.90%)  3
Hyponatraemia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 4/73 (5.48%)  4 1/69 (1.45%)  1
Hypophosphataemia  1  2/38 (5.26%)  3 1/11 (9.09%)  1 3/73 (4.11%)  3 0/69 (0.00%)  0
Hypocalcaemia  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 2/69 (2.90%)  3
Hypoalbuminaemia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Hypercalcaemia  1  0/38 (0.00%)  0 1/11 (9.09%)  4 0/73 (0.00%)  0 0/69 (0.00%)  0
Hyperkalaemia  1  4/38 (10.53%)  4 0/11 (0.00%)  0 1/73 (1.37%)  2 1/69 (1.45%)  1
Musculoskeletal and connective tissue disorders         
Myalgia  1  10/38 (26.32%)  15 2/11 (18.18%)  7 9/73 (12.33%)  11 9/69 (13.04%)  13
Arthralgia  1  11/38 (28.95%)  18 3/11 (27.27%)  3 7/73 (9.59%)  9 6/69 (8.70%)  9
Pain in extremity  1  7/38 (18.42%)  14 1/11 (9.09%)  1 8/73 (10.96%)  9 5/69 (7.25%)  6
Muscle spasms  1  3/38 (7.89%)  7 0/11 (0.00%)  0 4/73 (5.48%)  4 7/69 (10.14%)  9
Back pain  1  5/38 (13.16%)  10 1/11 (9.09%)  1 4/73 (5.48%)  4 3/69 (4.35%)  3
Musculoskeletal pain  1  2/38 (5.26%)  2 1/11 (9.09%)  1 3/73 (4.11%)  5 2/69 (2.90%)  2
Neck pain  1  3/38 (7.89%)  4 0/11 (0.00%)  0 4/73 (5.48%)  5 1/69 (1.45%)  1
Muscular weakness  1  6/38 (15.79%)  9 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  3
Flank pain  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 3/69 (4.35%)  3
Bone pain  1  2/38 (5.26%)  2 0/11 (0.00%)  0 2/73 (2.74%)  4 1/69 (1.45%)  1
Musculoskeletal chest pain  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Pain in jaw  1  3/38 (7.89%)  8 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Musculoskeletal discomfort  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Invasive ductal breast carcinoma  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Nervous system disorders         
Neuropathy peripheral  1  8/38 (21.05%)  8 4/11 (36.36%)  4 12/73 (16.44%)  15 13/69 (18.84%)  16
Headache  1  6/38 (15.79%)  9 1/11 (9.09%)  1 8/73 (10.96%)  11 13/69 (18.84%)  22
Dizziness  1  8/38 (21.05%)  14 0/11 (0.00%)  0 10/73 (13.70%)  16 6/69 (8.70%)  9
Peripheral sensory neuropathy  1  4/38 (10.53%)  4 2/11 (18.18%)  2 9/73 (12.33%)  9 8/69 (11.59%)  9
Dysgeusia  1  7/38 (18.42%)  9 0/11 (0.00%)  0 4/73 (5.48%)  4 5/69 (7.25%)  6
Somnolence  1  2/38 (5.26%)  3 1/11 (9.09%)  1 7/73 (9.59%)  9 0/69 (0.00%)  0
Paraesthesia  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 5/69 (7.25%)  8
Restless legs syndrome  1  3/38 (7.89%)  3 0/11 (0.00%)  0 3/73 (4.11%)  3 2/69 (2.90%)  2
Memory impairment  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 2/69 (2.90%)  2
Amnesia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 1/69 (1.45%)  1
Hyperaesthesia  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Tremor  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Product Issues         
Device malfunction  1  0/38 (0.00%)  0 1/11 (9.09%)  2 0/73 (0.00%)  0 0/69 (0.00%)  0
Psychiatric disorders         
Insomnia  1  6/38 (15.79%)  6 2/11 (18.18%)  2 8/73 (10.96%)  8 7/69 (10.14%)  8
Anxiety  1  3/38 (7.89%)  3 1/11 (9.09%)  1 11/73 (15.07%)  11 7/69 (10.14%)  9
Depression  1  4/38 (10.53%)  4 1/11 (9.09%)  1 6/73 (8.22%)  7 4/69 (5.80%)  4
Aggression  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Renal and urinary disorders         
Haematuria  1  1/38 (2.63%)  1 2/11 (18.18%)  2 3/73 (4.11%)  3 5/69 (7.25%)  5
Dysuria  1  2/38 (5.26%)  2 1/11 (9.09%)  1 4/73 (5.48%)  12 3/69 (4.35%)  9
Pollakiuria  1  2/38 (5.26%)  2 1/11 (9.09%)  1 3/73 (4.11%)  3 1/69 (1.45%)  1
Bladder spasm  1  3/38 (7.89%)  3 0/11 (0.00%)  0 2/73 (2.74%)  2 0/69 (0.00%)  0
Acute kidney injury  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Proteinuria  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Renal failure  1  2/38 (5.26%)  2 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Cystitis noninfective  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Reproductive system and breast disorders         
Vaginal haemorrhage  1  3/38 (7.89%)  4 0/11 (0.00%)  0 0/73 (0.00%)  0 2/69 (2.90%)  2
Genital discomfort  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Vulvovaginal pain  1  3/38 (7.89%)  3 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Cystocele  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Postmenopausal haemorrhage  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough  1  11/38 (28.95%)  13 3/11 (27.27%)  3 17/73 (23.29%)  20 4/69 (5.80%)  4
Dyspnoea  1  10/38 (26.32%)  11 3/11 (27.27%)  3 9/73 (12.33%)  10 11/69 (15.94%)  19
Epistaxis  1  7/38 (18.42%)  11 1/11 (9.09%)  1 6/73 (8.22%)  6 7/69 (10.14%)  11
Oropharyngeal pain  1  10/38 (26.32%)  12 1/11 (9.09%)  1 6/73 (8.22%)  7 2/69 (2.90%)  2
Nasal congestion  1  4/38 (10.53%)  5 1/11 (9.09%)  1 3/73 (4.11%)  5 0/69 (0.00%)  0
Rhinorrhoea  1  4/38 (10.53%)  4 1/11 (9.09%)  1 2/73 (2.74%)  2 0/69 (0.00%)  0
Pleural effusion  1  2/38 (5.26%)  2 1/11 (9.09%)  2 2/73 (2.74%)  2 1/69 (1.45%)  1
Dysphonia  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  1 1/69 (1.45%)  1
Rhinitis allergic  1  3/38 (7.89%)  3 0/11 (0.00%)  0 0/73 (0.00%)  0 1/69 (1.45%)  2
Hypoxia  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Pulmonary embolism  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 1/69 (1.45%)  1
Throat irritation  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Sinus disorder  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Skin and subcutaneous tissue disorders         
Alopecia  1  26/38 (68.42%)  29 5/11 (45.45%)  6 28/73 (38.36%)  36 22/69 (31.88%)  24
Rash  1  8/38 (21.05%)  9 2/11 (18.18%)  2 5/73 (6.85%)  5 2/69 (2.90%)  2
Dry skin  1  4/38 (10.53%)  4 1/11 (9.09%)  1 5/73 (6.85%)  5 2/69 (2.90%)  2
Pruritus  1  4/38 (10.53%)  5 0/11 (0.00%)  0 5/73 (6.85%)  5 2/69 (2.90%)  4
Erythema  1  5/38 (13.16%)  6 1/11 (9.09%)  1 2/73 (2.74%)  2 2/69 (2.90%)  4
Nail disorder  1  4/38 (10.53%)  4 3/11 (27.27%)  3 1/73 (1.37%)  1 0/69 (0.00%)  0
Onycholysis  1  2/38 (5.26%)  2 0/11 (0.00%)  0 2/73 (2.74%)  2 3/69 (4.35%)  3
Skin lesion  1  6/38 (15.79%)  12 0/11 (0.00%)  0 1/73 (1.37%)  3 0/69 (0.00%)  0
Skin exfoliation  1  4/38 (10.53%)  4 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  1/38 (2.63%)  1 1/11 (9.09%)  1 2/73 (2.74%)  2 0/69 (0.00%)  0
Pruritus generalised  1  2/38 (5.26%)  2 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Rash macular  1  2/38 (5.26%)  2 0/11 (0.00%)  0 1/73 (1.37%)  4 1/69 (1.45%)  1
Rash pruritic  1  3/38 (7.89%)  3 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Nail discolouration  1  0/38 (0.00%)  0 1/11 (9.09%)  1 2/73 (2.74%)  2 0/69 (0.00%)  0
Rash erythematous  1  2/38 (5.26%)  3 0/11 (0.00%)  0 1/73 (1.37%)  1 0/69 (0.00%)  0
Dermatitis contact  1  1/38 (2.63%)  1 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Hyperhidrosis  1  2/38 (5.26%)  3 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Skin ulcer  1  2/38 (5.26%)  10 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Solar dermatitis  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Vascular disorders         
Flushing  1  2/38 (5.26%)  2 1/11 (9.09%)  1 3/73 (4.11%)  5 1/69 (1.45%)  2
Hot flush  1  3/38 (7.89%)  4 0/11 (0.00%)  0 1/73 (1.37%)  1 2/69 (2.90%)  3
Hypotension  1  0/38 (0.00%)  0 0/11 (0.00%)  0 4/73 (5.48%)  5 2/69 (2.90%)  2
Deep vein thrombosis  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 1/69 (1.45%)  1
Lymphoedema  1  1/38 (2.63%)  1 1/11 (9.09%)  1 1/73 (1.37%)  1 0/69 (0.00%)  0
Orthostatic hypotension  1  3/38 (7.89%)  3 0/11 (0.00%)  0 0/73 (0.00%)  0 0/69 (0.00%)  0
Blood pressure fluctuation  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Superior vena cava stenosis  1  0/38 (0.00%)  0 1/11 (9.09%)  1 0/73 (0.00%)  0 0/69 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
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.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01091428     History of Changes
Other Study ID Numbers: C14008
2009-011428-79 ( EudraCT Number )
U1111-1191-6584 ( Registry Identifier: WHO )
First Submitted: March 17, 2010
First Posted: March 24, 2010
Results First Submitted: February 21, 2018
Results First Posted: June 4, 2018
Last Update Posted: June 4, 2018