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A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Paclitaxel in Women With Endometrial Cancer

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: NCT02725268
Recruitment Status : Completed
First Posted : March 31, 2016
Results First Posted : June 9, 2020
Last Update Posted : November 27, 2020
Sponsor:
Collaborators:
European Network of Translational Research in Ovarian Cancer - EUTROC
European Network of Individualized Treatment in Endometrial Cancer - ENITEC
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Endometrial Neoplasms
Interventions Drug: Paclitaxel
Drug: Sapanisertib
Drug: MLN1117
Enrollment 241
Recruitment Details Participants took part in the study at 60 investigative sites in Australia, Belgium, Germany, Italy, Netherlands, Norway, Spain, United Kingdom, Canada and the United States from 08 September 2016 to 23 July 2019.
Pre-assignment Details The female participants with a diagnosis of endometrial carcinoma were enrolled and randomized into 1:1:1:1 ratio to receive single agent paclitaxel, paclitaxel in combination with sapanisertib, single agent sapanisertib or sapanisertib in combination with MLN1117.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks). Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks). Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks). Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Period Title: Overall Study
Started 90 90 41 20
Completed 31 31 4 3
Not Completed 59 59 37 17
Reason Not Completed
Death             45             48             29             16
Lost to Follow-up             2             3             0             0
Withdrawal by Subject             8             4             8             1
Reason not Specified             1             1             0             0
Ongoing             3             3             0             0
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg Total
Hide Arm/Group Description Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks). Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks). Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks). Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks). Total of all reporting groups
Overall Number of Baseline Participants 90 90 41 20 241
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
63.7  (7.14) 64.4  (7.63) 64.0  (6.99) 62.0  (10.20) 63.9  (7.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
Female
90
 100.0%
90
 100.0%
41
 100.0%
20
 100.0%
241
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
Hispanic or Latino
3
   3.3%
5
   5.6%
3
   7.3%
4
  20.0%
15
   6.2%
Not Hispanic or Latino
84
  93.3%
80
  88.9%
37
  90.2%
15
  75.0%
216
  89.6%
Unknown or Not Reported
3
   3.3%
5
   5.6%
1
   2.4%
1
   5.0%
10
   4.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
White
77
  85.6%
78
  86.7%
37
  90.2%
18
  90.0%
210
  87.1%
Black or African American
3
   3.3%
4
   4.4%
0
   0.0%
1
   5.0%
8
   3.3%
Native Hawaiian or other Pacific Islander
1
   1.1%
0
   0.0%
1
   2.4%
0
   0.0%
2
   0.8%
Asian
6
   6.7%
3
   3.3%
1
   2.4%
1
   5.0%
11
   4.6%
Other
0
   0.0%
2
   2.2%
2
   4.9%
0
   0.0%
4
   1.7%
Not Reported
3
   3.3%
3
   3.3%
0
   0.0%
0
   0.0%
6
   2.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Australia Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
5
   5.6%
6
   6.7%
3
   7.3%
2
  10.0%
16
   6.6%
Belgium Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
5
   5.6%
10
  11.1%
2
   4.9%
3
  15.0%
20
   8.3%
Germany Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
6
   6.7%
4
   4.4%
1
   2.4%
0
   0.0%
11
   4.6%
Italy Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
14
  15.6%
22
  24.4%
9
  22.0%
4
  20.0%
49
  20.3%
Netherlands Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
2
   2.2%
3
   3.3%
0
   0.0%
0
   0.0%
5
   2.1%
Norway Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
3
   3.3%
1
   1.1%
1
   2.4%
0
   0.0%
5
   2.1%
Spain Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
10
  11.1%
7
   7.8%
5
  12.2%
6
  30.0%
28
  11.6%
United Kingdom Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
9
  10.0%
4
   4.4%
6
  14.6%
2
  10.0%
21
   8.7%
Canada Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
15
  16.7%
10
  11.1%
2
   4.9%
0
   0.0%
27
  11.2%
United States Number Analyzed 90 participants 90 participants 41 participants 20 participants 241 participants
21
  23.3%
23
  25.6%
12
  29.3%
3
  15.0%
59
  24.5%
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 87 participants 83 participants 41 participants 20 participants 231 participants
160.60  (6.335) 160.26  (5.771) 159.01  (6.471) 162.67  (5.854) 160.37  (6.149)
[1]
Measure Analysis Population Description: Number analyzed is the number of participants with height data at Baseline.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 87 participants 85 participants 41 participants 20 participants 233 participants
72.77  (19.118) 72.28  (18.376) 75.35  (17.969) 71.81  (18.613) 72.96  (18.523)
[1]
Measure Analysis Population Description: Number analyzed is the number of participants with weight data at Baseline.
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. For a participant who had not progressed and was last known to be alive, PFS was censored at the last response assessment that is stable disease (SD) or better.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 90 90 41 20
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(2.3 to 4.3)
5.6
(3.8 to 6.2)
2.1
(1.9 to 3.5)
2.0
(1.5 to 3.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval 95%
0.58 to 1.15
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.84
Confidence Interval 95%
1.18 to 2.85
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.56
Confidence Interval 95%
1.46 to 4.48
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
2.Secondary Outcome
Title Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame From the first dose of study drug through 30 days after the last dose of study drug (Up to 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study drug.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 87 86 41 20
Measure Type: Count of Participants
Unit of Measure: Participants
87
 100.0%
86
 100.0%
41
 100.0%
20
 100.0%
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time in months from the date of randomization to the date of death.
Time Frame Up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 90 90 41 20
Median (95% Confidence Interval)
Unit of Measure: months
14.6
(9.8 to 22.0)
13.7
(9.6 to 20.5)
12.5
(9.0 to 15.7)
11.1
(2.7 to 17.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.954
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.67 to 1.53
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.212
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.90 to 2.33
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.352
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.43
Confidence Interval 95%
0.79 to 2.57
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
4.Secondary Outcome
Title Time to Tumor Progression (TTP)
Hide Description TTP is defined as the time in months from the date of randomization to the date of first documentation of progression. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. For a participant who has not progressed, TTP was censored at the last response assessment that is SD or better.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 90 90 41 20
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(2.5 to 5.4)
5.7
(3.8 to 7.2)
2.3
(1.9 to 4.2)
2.2
(1.8 to 3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval 95%
0.58 to 1.16
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.208
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
1.06 to 2.73
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.221
Comments The p-value was obtained using stratified log-rank test with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.32
Confidence Interval 95%
1.34 to 4.03
Estimation Comments The hazard ratio was obtained using a stratified Cox proportional hazard model adjusted for histological subtype, lines of prior chemotherapy and prior taxane therapy. A hazard ratio of <1 was considered statistically significant.
5.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants who achieved a best response of a complete response (CR) or partial response (PR). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least 1 dose of study drug.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 87 86 41 20
Measure Type: Number
Unit of Measure: percentage of participants
18.4 24.4 4.9 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.34
Confidence Interval 95%
0.64 to 2.81
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified Cochran-Mantel-Haenszel (CMH) model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.04 to 1.19
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.00
Confidence Interval 95%
0.00 to 0.00
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
6.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description CBR is defined as the percentage of participants with CR or PR or SD (SD of any duration). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least 1 dose of study drug.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 87 86 41 20
Measure Type: Number
Unit of Measure: percentage of participants
57.5 80.2 34.1 35.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.84
Confidence Interval 95%
1.43 to 5.63
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.42
Confidence Interval 95%
0.19 to 0.92
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.47
Confidence Interval 95%
0.16 to 1.37
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
7.Secondary Outcome
Title Clinical Benefit Rate (CBR) at Week 16 (CBR-16)
Hide Description CBR-16 is defined as the percentage of participants who achieved CR or PR of any duration or have SD with a duration of at least 16 weeks. Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least 1 dose of study drug.
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description:
Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Overall Number of Participants Analyzed 87 86 41 20
Measure Type: Number
Unit of Measure: percentage of participants
36.8 51.2 17.1 5.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.62
Confidence Interval 95%
0.89 to 7.67
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.15
Confidence Interval 95%
0.05 to 0.51
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel 80 mg/m^2, Sapanisertib 4 mg + MLN1117 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.07
Confidence Interval 95%
0.01 to 0.67
Estimation Comments The odds ratio and 95% confidence intervals were obtained using a stratified CMH model with histological subtype, lines of prior chemotherapy and prior taxane therapy (original stratification values).
Time Frame All-Cause Mortality: Up to the end of study (approximately 36 months); SAEs and other AEs: From first dose through 30 days after the last dose of study drug (Up to 31 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. All-cause mortality population is based on ITT population. Serious and other adverse events were collected for Safety population.
 
Arm/Group Title Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Hide Arm/Group Description Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks). Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks). Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks). Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
All-Cause Mortality
Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   45/90 (50.00%)   48/90 (53.33%)   29/41 (70.73%)   16/20 (80.00%) 
Hide Serious Adverse Events
Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/87 (26.44%)   47/86 (54.65%)   14/41 (34.15%)   7/20 (35.00%) 
Blood and lymphatic system disorders         
Febrile neutropenia  1  2/87 (2.30%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Anaemia  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Cardiac disorders         
Acute myocardial infarction  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Atrial tachycardia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Tachycardia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Gastrointestinal disorders         
Nausea  1  0/87 (0.00%)  2/86 (2.33%)  2/41 (4.88%)  2/20 (10.00%) 
Vomiting  1  0/87 (0.00%)  2/86 (2.33%)  2/41 (4.88%)  2/20 (10.00%) 
Intestinal obstruction  1  3/87 (3.45%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Small intestinal obstruction  1  2/87 (2.30%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Abdominal pain  1  2/87 (2.30%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Colitis  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Intestinal perforation  1  0/87 (0.00%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Large intestinal obstruction  1  2/87 (2.30%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Subileus  1  2/87 (2.30%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Abdominal distension  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Abdominal hernia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Abdominal pain lower  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Constipation  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Diarrhoea  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Discoloured vomit  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Dyspepsia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Faecaloma  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Haematemesis  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Ileus  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
General disorders         
General physical health deterioration  1  3/87 (3.45%)  3/86 (3.49%)  1/41 (2.44%)  1/20 (5.00%) 
Fatigue  1  0/87 (0.00%)  2/86 (2.33%)  1/41 (2.44%)  1/20 (5.00%) 
Pyrexia  1  1/87 (1.15%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Malaise  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Pain  1  1/87 (1.15%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Asthenia  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Death  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Non-cardiac chest pain  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Hepatobiliary disorders         
Hepatic failure  1  2/87 (2.30%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Hyperbilirubinaemia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Infections and infestations         
Sepsis  1  1/87 (1.15%)  3/86 (3.49%)  0/41 (0.00%)  0/20 (0.00%) 
Pneumonia  1  0/87 (0.00%)  3/86 (3.49%)  0/41 (0.00%)  0/20 (0.00%) 
Urinary tract infection  1  0/87 (0.00%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Abdominal abscess  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Bacteraemia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Cellulitis  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Cystitis  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Enterocolitis infectious  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Gastroenteritis  1  0/87 (0.00%)  0/86 (0.00%)  0/41 (0.00%)  1/20 (5.00%) 
Kidney infection  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Lung infection  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Pyelonephritis  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Staphylococcal infection  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Urosepsis  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Vaginal infection  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Injury, poisoning and procedural complications         
Foot fracture  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Lower limb fracture  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Overdose  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Urinary tract stoma complication  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Investigations         
Blood glucose increased  1  0/87 (0.00%)  0/86 (0.00%)  0/41 (0.00%)  1/20 (5.00%) 
Electrocardiogram QT prolonged  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Platelet count decreased  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Transaminases increased  1  0/87 (0.00%)  0/86 (0.00%)  0/41 (0.00%)  1/20 (5.00%) 
Waist circumference increased  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Hyperglycaemia  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Hypokalaemia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Fistula  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Endometrial cancer  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  1/20 (5.00%) 
Malignant ascites  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Metastases to central nervous system  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Nervous system disorders         
Cerebrovascular accident  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Encephalopathy  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Ischaemic stroke  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Spinal cord compression  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Syncope  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Psychiatric disorders         
Confusional state  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  1/87 (1.15%)  1/86 (1.16%)  1/41 (2.44%)  0/20 (0.00%) 
Haematuria  1  1/87 (1.15%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Urinary tract obstruction  1  1/87 (1.15%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Hydronephrosis  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Renal failure  1  0/87 (0.00%)  0/86 (0.00%)  1/41 (2.44%)  0/20 (0.00%) 
Reproductive system and breast disorders         
Vaginal haemorrhage  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism  1  0/87 (0.00%)  4/86 (4.65%)  0/41 (0.00%)  0/20 (0.00%) 
Dyspnoea  1  0/87 (0.00%)  3/86 (3.49%)  0/41 (0.00%)  0/20 (0.00%) 
Pneumonitis  1  0/87 (0.00%)  3/86 (3.49%)  0/41 (0.00%)  0/20 (0.00%) 
Respiratory failure  1  0/87 (0.00%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Acute respiratory failure  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Dyspnoea exertional  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Hypoxia  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Pleural effusion  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash generalised  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
Vascular disorders         
Hypotension  1  1/87 (1.15%)  0/86 (0.00%)  0/41 (0.00%)  0/20 (0.00%) 
Lymphoedema  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paclitaxel 80 mg/m^2 Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg Sapanisertib 30 mg Sapanisertib 4 mg + MLN1117 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/87 (97.70%)   86/86 (100.00%)   41/41 (100.00%)   20/20 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  32/87 (36.78%)  48/86 (55.81%)  5/41 (12.20%)  6/20 (30.00%) 
Neutropenia  1  10/87 (11.49%)  19/86 (22.09%)  1/41 (2.44%)  1/20 (5.00%) 
Leukopenia  1  8/87 (9.20%)  12/86 (13.95%)  0/41 (0.00%)  1/20 (5.00%) 
Cardiac disorders         
Tachycardia  1  1/87 (1.15%)  6/86 (6.98%)  3/41 (7.32%)  0/20 (0.00%) 
Ear and labyrinth disorders         
Vertigo  1  2/87 (2.30%)  4/86 (4.65%)  0/41 (0.00%)  2/20 (10.00%) 
Gastrointestinal disorders         
Nausea  1  29/87 (33.33%)  52/86 (60.47%)  30/41 (73.17%)  16/20 (80.00%) 
Diarrhoea  1  31/87 (35.63%)  48/86 (55.81%)  15/41 (36.59%)  13/20 (65.00%) 
Vomiting  1  20/87 (22.99%)  24/86 (27.91%)  31/41 (75.61%)  15/20 (75.00%) 
Constipation  1  25/87 (28.74%)  20/86 (23.26%)  14/41 (34.15%)  5/20 (25.00%) 
Abdominal pain  1  13/87 (14.94%)  22/86 (25.58%)  6/41 (14.63%)  4/20 (20.00%) 
Stomatitis  1  4/87 (4.60%)  22/86 (25.58%)  10/41 (24.39%)  2/20 (10.00%) 
Abdominal pain upper  1  6/87 (6.90%)  13/86 (15.12%)  4/41 (9.76%)  4/20 (20.00%) 
Dyspepsia  1  5/87 (5.75%)  13/86 (15.12%)  3/41 (7.32%)  1/20 (5.00%) 
Gastrooesophageal reflux disease  1  4/87 (4.60%)  10/86 (11.63%)  3/41 (7.32%)  3/20 (15.00%) 
Dry mouth  1  2/87 (2.30%)  8/86 (9.30%)  2/41 (4.88%)  2/20 (10.00%) 
Abdominal distension  1  4/87 (4.60%)  6/86 (6.98%)  1/41 (2.44%)  0/20 (0.00%) 
Abdominal pain lower  1  4/87 (4.60%)  3/86 (3.49%)  0/41 (0.00%)  3/20 (15.00%) 
Haemorrhoids  1  5/87 (5.75%)  2/86 (2.33%)  1/41 (2.44%)  0/20 (0.00%) 
General disorders         
Fatigue  1  39/87 (44.83%)  40/86 (46.51%)  18/41 (43.90%)  7/20 (35.00%) 
Asthenia  1  7/87 (8.05%)  25/86 (29.07%)  9/41 (21.95%)  10/20 (50.00%) 
Pyrexia  1  12/87 (13.79%)  13/86 (15.12%)  5/41 (12.20%)  4/20 (20.00%) 
Oedema peripheral  1  18/87 (20.69%)  9/86 (10.47%)  2/41 (4.88%)  1/20 (5.00%) 
Peripheral swelling  1  5/87 (5.75%)  5/86 (5.81%)  0/41 (0.00%)  2/20 (10.00%) 
Chills  1  1/87 (1.15%)  5/86 (5.81%)  0/41 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Urinary tract infection  1  9/87 (10.34%)  18/86 (20.93%)  6/41 (14.63%)  3/20 (15.00%) 
Upper respiratory tract infection  1  8/87 (9.20%)  6/86 (6.98%)  1/41 (2.44%)  0/20 (0.00%) 
Nasopharyngitis  1  2/87 (2.30%)  5/86 (5.81%)  2/41 (4.88%)  0/20 (0.00%) 
Sinusitis  1  5/87 (5.75%)  2/86 (2.33%)  0/41 (0.00%)  0/20 (0.00%) 
Investigations         
Weight decreased  1  2/87 (2.30%)  16/86 (18.60%)  7/41 (17.07%)  3/20 (15.00%) 
Gamma-glutamyltransferase increased  1  6/87 (6.90%)  9/86 (10.47%)  5/41 (12.20%)  0/20 (0.00%) 
Alanine aminotransferase increased  1  5/87 (5.75%)  7/86 (8.14%)  1/41 (2.44%)  6/20 (30.00%) 
Aspartate aminotransferase increased  1  3/87 (3.45%)  7/86 (8.14%)  2/41 (4.88%)  6/20 (30.00%) 
Neutrophil count decreased  1  8/87 (9.20%)  9/86 (10.47%)  0/41 (0.00%)  0/20 (0.00%) 
Blood creatinine increased  1  3/87 (3.45%)  6/86 (6.98%)  3/41 (7.32%)  4/20 (20.00%) 
White blood cell count decreased  1  5/87 (5.75%)  9/86 (10.47%)  1/41 (2.44%)  0/20 (0.00%) 
Blood alkaline phosphatase increased  1  4/87 (4.60%)  5/86 (5.81%)  4/41 (9.76%)  0/20 (0.00%) 
Platelet count decreased  1  2/87 (2.30%)  2/86 (2.33%)  1/41 (2.44%)  2/20 (10.00%) 
Protein total decreased  1  1/87 (1.15%)  1/86 (1.16%)  3/41 (7.32%)  1/20 (5.00%) 
Blood glucose increased  1  0/87 (0.00%)  0/86 (0.00%)  0/41 (0.00%)  2/20 (10.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  16/87 (18.39%)  33/86 (38.37%)  20/41 (48.78%)  8/20 (40.00%) 
Hyperglycaemia  1  8/87 (9.20%)  17/86 (19.77%)  15/41 (36.59%)  5/20 (25.00%) 
Hypomagnesaemia  1  11/87 (12.64%)  19/86 (22.09%)  7/41 (17.07%)  1/20 (5.00%) 
Hypokalaemia  1  6/87 (6.90%)  10/86 (11.63%)  3/41 (7.32%)  0/20 (0.00%) 
Dehydration  1  1/87 (1.15%)  8/86 (9.30%)  6/41 (14.63%)  2/20 (10.00%) 
Hypophosphataemia  1  2/87 (2.30%)  12/86 (13.95%)  2/41 (4.88%)  1/20 (5.00%) 
Hypoalbuminaemia  1  3/87 (3.45%)  8/86 (9.30%)  4/41 (9.76%)  1/20 (5.00%) 
Hyponatraemia  1  3/87 (3.45%)  6/86 (6.98%)  4/41 (9.76%)  2/20 (10.00%) 
Hypocalcaemia  1  2/87 (2.30%)  6/86 (6.98%)  1/41 (2.44%)  2/20 (10.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  11/87 (12.64%)  21/86 (24.42%)  0/41 (0.00%)  0/20 (0.00%) 
Back pain  1  14/87 (16.09%)  10/86 (11.63%)  3/41 (7.32%)  3/20 (15.00%) 
Pain in extremity  1  7/87 (8.05%)  16/86 (18.60%)  1/41 (2.44%)  1/20 (5.00%) 
Myalgia  1  12/87 (13.79%)  10/86 (11.63%)  1/41 (2.44%)  1/20 (5.00%) 
Muscular weakness  1  4/87 (4.60%)  9/86 (10.47%)  0/41 (0.00%)  1/20 (5.00%) 
Groin pain  1  0/87 (0.00%)  1/86 (1.16%)  0/41 (0.00%)  2/20 (10.00%) 
Nervous system disorders         
Neuropathy peripheral  1  12/87 (13.79%)  22/86 (25.58%)  3/41 (7.32%)  0/20 (0.00%) 
Dysgeusia  1  10/87 (11.49%)  14/86 (16.28%)  6/41 (14.63%)  2/20 (10.00%) 
Headache  1  4/87 (4.60%)  13/86 (15.12%)  6/41 (14.63%)  1/20 (5.00%) 
Dizziness  1  3/87 (3.45%)  14/86 (16.28%)  3/41 (7.32%)  2/20 (10.00%) 
Paraesthesia  1  6/87 (6.90%)  9/86 (10.47%)  1/41 (2.44%)  1/20 (5.00%) 
Peripheral sensory neuropathy  1  6/87 (6.90%)  8/86 (9.30%)  0/41 (0.00%)  0/20 (0.00%) 
Taste disorder  1  2/87 (2.30%)  6/86 (6.98%)  2/41 (4.88%)  0/20 (0.00%) 
Tremor  1  2/87 (2.30%)  4/86 (4.65%)  3/41 (7.32%)  1/20 (5.00%) 
Psychiatric disorders         
Insomnia  1  6/87 (6.90%)  17/86 (19.77%)  1/41 (2.44%)  1/20 (5.00%) 
Anxiety  1  3/87 (3.45%)  7/86 (8.14%)  3/41 (7.32%)  1/20 (5.00%) 
Depression  1  3/87 (3.45%)  3/86 (3.49%)  5/41 (12.20%)  0/20 (0.00%) 
Renal and urinary disorders         
Haematuria  1  6/87 (6.90%)  8/86 (9.30%)  0/41 (0.00%)  0/20 (0.00%) 
Dysuria  1  5/87 (5.75%)  6/86 (6.98%)  0/41 (0.00%)  1/20 (5.00%) 
Proteinuria  1  1/87 (1.15%)  5/86 (5.81%)  0/41 (0.00%)  0/20 (0.00%) 
Reproductive system and breast disorders         
Vaginal haemorrhage  1  6/87 (6.90%)  4/86 (4.65%)  0/41 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  18/87 (20.69%)  24/86 (27.91%)  6/41 (14.63%)  3/20 (15.00%) 
Cough  1  21/87 (24.14%)  19/86 (22.09%)  8/41 (19.51%)  1/20 (5.00%) 
Epistaxis  1  6/87 (6.90%)  11/86 (12.79%)  1/41 (2.44%)  0/20 (0.00%) 
Pulmonary embolism  1  3/87 (3.45%)  10/86 (11.63%)  3/41 (7.32%)  0/20 (0.00%) 
Oropharyngeal pain  1  3/87 (3.45%)  4/86 (4.65%)  3/41 (7.32%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  31/87 (35.63%)  27/86 (31.40%)  1/41 (2.44%)  0/20 (0.00%) 
Rash  1  5/87 (5.75%)  15/86 (17.44%)  4/41 (9.76%)  0/20 (0.00%) 
Pruritus  1  2/87 (2.30%)  11/86 (12.79%)  6/41 (14.63%)  1/20 (5.00%) 
Dry skin  1  6/87 (6.90%)  8/86 (9.30%)  0/41 (0.00%)  1/20 (5.00%) 
Rash maculo-papular  1  5/87 (5.75%)  2/86 (2.33%)  1/41 (2.44%)  0/20 (0.00%) 
Vascular disorders         
Hypertension  1  9/87 (10.34%)  5/86 (5.81%)  2/41 (4.88%)  1/20 (5.00%) 
Deep vein thrombosis  1  3/87 (3.45%)  5/86 (5.81%)  0/41 (0.00%)  1/20 (5.00%) 
Hypotension  1  2/87 (2.30%)  6/86 (6.98%)  0/41 (0.00%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA 22.0
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.
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: +1-866-835-2233
EMail: globaloncologymedinfo@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02725268    
Other Study ID Numbers: C31004
U1111-1168-1824 ( Other Identifier: WHO )
2014-005394-37 ( EudraCT Number )
02725268 ( Registry Identifier: ClinicalTrials.gov )
First Submitted: March 28, 2016
First Posted: March 31, 2016
Results First Submitted: May 22, 2020
Results First Posted: June 9, 2020
Last Update Posted: November 27, 2020