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A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT02301988
Recruitment Status : Completed
First Posted : November 26, 2014
Results First Posted : September 20, 2018
Last Update Posted : October 17, 2018
Sponsor:
Collaborator:
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Ipatasertib
Drug: Paclitaxel
Drug: Placebo
Enrollment 151
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Period Title: Overall Study
Started 76 75
Completed 66 66
Not Completed 10 9
Reason Not Completed
Withdrawal by Subject             2             1
Physician Decision             2             2
Unknown Reason             1             3
Lack of Efficacy             3             2
Death             1             0
Adverse Event             1             1
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel Total
Hide Arm/Group Description Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses). Total of all reporting groups
Overall Number of Baseline Participants 76 75 151
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, with participants allocated to the treatment arms to which they were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 76 participants 75 participants 151 participants
53.8  (10.9) 53.8  (12.0) 53.8  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 75 participants 151 participants
Female
76
 100.0%
75
 100.0%
151
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 75 participants 151 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   1.3%
1
   0.7%
Native Hawaiian or Other Pacific Islander
1
   1.3%
0
   0.0%
1
   0.7%
Black or African American
2
   2.6%
3
   4.0%
5
   3.3%
White
71
  93.4%
70
  93.3%
141
  93.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   2.6%
1
   1.3%
3
   2.0%
1.Primary Outcome
Title Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants)
Hide Description pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.1
(9.82 to 27.25)
13.3
(6.58 to 22.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.519
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 3.77
Confidence Interval 95%
-8.99 to 16.54
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
2.Primary Outcome
Title Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors)
Hide Description pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who have PTEN-low tumors.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 19 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.8
(4.45 to 38.36)
12.5
(2.27 to 35.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7817
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 3.29
Confidence Interval (2-Sided) 95%
-25.52 to 32.10
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
3.Secondary Outcome
Title Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)
Hide Description pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.4
(14.33 to 33.31)
14.7
(7.98 to 24.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2234
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 7.70
Confidence Interval (2-Sided) 95%
-5.95 to 21.35
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
4.Secondary Outcome
Title Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors)
Hide Description pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who have PTEN-low tumors.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 19 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.8
(4.45 to 38.36)
18.8
(5.31 to 42.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8169
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -2.96
Confidence Interval (2-Sided) 95%
-33.91 to 27.99
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
5.Secondary Outcome
Title Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants)
Hide Description Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
67.1
(55.86 to 77.46)
56.0
(44.46 to 66.84)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1607
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value 11.11
Confidence Interval 95%
-5.64 to 27.85
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
6.Secondary Outcome
Title Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)
Hide Description ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who have PTEN-low tumors.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 19 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
73.7
(50.00 to 89.01)
50.0
(27.20 to 72.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments Unstratified Analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1486
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 23.68
Confidence Interval (2-Sided) 95%
-13.57 to 60.94
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.
7.Secondary Outcome
Title Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+])
Hide Description pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who are Akt Dx+.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 28 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.9
(7.31 to 35.71)
11.8
(4.12 to 27.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4980
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 6.09
Confidence Interval (2-Sided) 95%
-15.01 to 27.20
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.
8.Secondary Outcome
Title Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+)
Hide Description pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who are Akt Dx+.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 28 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.4
(9.77 to 40.58)
11.8
(4.12 to 27.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3032
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 9.66
Confidence Interval 95%
-12.25 to 31.58
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.
9.Secondary Outcome
Title Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype
Hide Description pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76 75
Measure Type: Number
Unit of Measure: percentage of participants
Unknown Number Analyzed 27 participants 32 participants
18.5 21.9
Basal Number Analyzed 41 participants 37 participants
22.0 10.8
Her2 Number Analyzed 6 participants 3 participants
33.3 0
LumA Number Analyzed 0 participants 1 participants
0
Normal Number Analyzed 2 participants 2 participants
50.0 0
10.Secondary Outcome
Title Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors
Hide Description After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time Frame Surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants with T2 or T3 Tumors.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 62 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.5
(51.93 to 76.26)
60.3
(47.20 to 71.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6280
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 4.20
Confidence Interval (2-Sided) 95%
-14.37 to 22.76
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.
11.Secondary Outcome
Title Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors
Hide Description After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time Frame From screening to surgery visit (at approximately Weeks 14 to 19)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants with T2 or T3 Tumors with response to conversion to BCS.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 12 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(12.29 to 65.11)
25
(9.03 to 50.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipatasertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6291
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 8.33
Confidence Interval (2-Sided) 95%
-33.04 to 49.71
Estimation Comments 95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.
12.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame Screening up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was identical to the ITT population and included all randomized participants.
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76 75
Measure Type: Number
Unit of Measure: percentage of participants
100 98.7
13.Secondary Outcome
Title Plasma Concentrations of Ipatasertib on Day 1 and Day 8
Hide Description Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time Frame 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants. Reported here are data for participants with data available.
Arm/Group Title Ipatasertib + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.5 hours Number Analyzed 73 participants
290  (312)
4 hours Number Analyzed 72 participants
196  (93.0)
166 hours Number Analyzed 71 participants
37.5  (28.3)
170 hours Number Analyzed 71 participants
355  (204)
14.Secondary Outcome
Title Minimum Observed Plasma Concentration (Cmin) of Ipatasertib
Hide Description Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.
Time Frame 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants.
Arm/Group Title Ipatasertib + Paclitaxel
Hide Arm/Group Description:
Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Overall Number of Participants Analyzed 76
Mean (Standard Deviation)
Unit of Measure: ng/mL
37.5  (28.3)
Time Frame 2 years and 6 months
Adverse Event Reporting Description The safety population was identical to the ITT population. The ITT population comprised all 151 randomized patients.
 
Arm/Group Title Ipatasertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
All-Cause Mortality
Ipatasertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   1/76 (1.32%)   0/75 (0.00%) 
Hide Serious Adverse Events
Ipatasertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   10/76 (13.16%)   3/75 (4.00%) 
Blood and lymphatic system disorders     
Sickle cell anaemia with crisis † 1  1/76 (1.32%)  0/75 (0.00%) 
Gastrointestinal disorders     
Diarrhoea † 1  1/76 (1.32%)  0/75 (0.00%) 
General disorders     
Pyrexia † 1  1/76 (1.32%)  1/75 (1.33%) 
Chest pain † 1  1/76 (1.32%)  0/75 (0.00%) 
Complication associated with device † 1  1/76 (1.32%)  0/75 (0.00%) 
General physical health deterioration † 1  0/76 (0.00%)  1/75 (1.33%) 
Infections and infestations     
Device related infection † 1  2/76 (2.63%)  0/75 (0.00%) 
Pneumonia † 1  1/76 (1.32%)  1/75 (1.33%) 
Atypical pneumonia † 1  1/76 (1.32%)  0/75 (0.00%) 
Metabolism and nutrition disorders     
Dehydration † 1  1/76 (1.32%)  0/75 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonitis † 1  1/76 (1.32%)  0/75 (0.00%) 
1
Term from vocabulary, MedDRA, version 20.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipatasertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   76/76 (100.00%)   73/75 (97.33%) 
Blood and lymphatic system disorders     
Anaemia † 1  14/76 (18.42%)  11/75 (14.67%) 
Neutropenia † 1  7/76 (9.21%)  6/75 (8.00%) 
Eye disorders     
Dry eye † 1  3/76 (3.95%)  4/75 (5.33%) 
Lacrimation increased † 1  4/76 (5.26%)  1/75 (1.33%) 
Gastrointestinal disorders     
Abdominal distension † 1  4/76 (5.26%)  1/75 (1.33%) 
Abdominal Pain † 1  14/76 (18.42%)  6/75 (8.00%) 
Abdominal pain upper † 1  7/76 (9.21%)  4/75 (5.33%) 
Constipation † 1  10/76 (13.16%)  16/75 (21.33%) 
Diarrhoea † 1  66/76 (86.84%)  24/75 (32.00%) 
Dry mouth † 1  7/76 (9.21%)  6/75 (8.00%) 
Gastrooesophageal reflux disease † 1  5/76 (6.58%)  8/75 (10.67%) 
Dyspepsia † 1  12/76 (15.79%)  9/75 (12.00%) 
Nausea † 1  36/76 (47.37%)  23/75 (30.67%) 
Stomatitis † 1  5/76 (6.58%)  6/75 (8.00%) 
Vomiting † 1  17/76 (22.37%)  4/75 (5.33%) 
General disorders     
Asthenia † 1  32/76 (42.11%)  29/75 (38.67%) 
Fatigue † 1  23/76 (30.26%)  24/75 (32.00%) 
Mucosal dryness † 1  4/76 (5.26%)  0/75 (0.00%) 
Mucosal inflammation † 1  14/76 (18.42%)  5/75 (6.67%) 
Oedema peripheral † 1  3/76 (3.95%)  5/75 (6.67%) 
Pyrexia † 1  8/76 (10.53%)  4/75 (5.33%) 
Infections and infestations     
Conjunctivitis † 1  2/76 (2.63%)  5/75 (6.67%) 
Folliculitis † 1  5/76 (6.58%)  3/75 (4.00%) 
Upper respiratory tract infection † 1  3/76 (3.95%)  5/75 (6.67%) 
Urinary tract infection † 1  8/76 (10.53%)  9/75 (12.00%) 
Viral upper respiratory tract infection † 1  4/76 (5.26%)  7/75 (9.33%) 
Injury, poisoning and procedural complications     
Infusion related reaction † 1  5/76 (6.58%)  4/75 (5.33%) 
Investigations     
Alanine aminotransferase increased † 1  5/76 (6.58%)  5/75 (6.67%) 
Aspartate aminotransferase increased † 1  3/76 (3.95%)  4/75 (5.33%) 
Neutrophil count decreased † 1  4/76 (5.26%)  4/75 (5.33%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  11/76 (14.47%)  6/75 (8.00%) 
Hyperglycaemia † 1  3/76 (3.95%)  5/75 (6.67%) 
Hypokalaemia † 1  4/76 (5.26%)  2/75 (2.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  8/76 (10.53%)  6/75 (8.00%) 
Musculoskeletal pain † 1  5/76 (6.58%)  3/75 (4.00%) 
Myalgia † 1  6/76 (7.89%)  12/75 (16.00%) 
Pain in extremity † 1  4/76 (5.26%)  7/75 (9.33%) 
Nervous system disorders     
Dizziness † 1  7/76 (9.21%)  8/75 (10.67%) 
Dysgeusia † 1  18/76 (23.68%)  17/75 (22.67%) 
Hypoaesthesia † 1  1/76 (1.32%)  4/75 (5.33%) 
Neuropathy peripheral † 1  14/76 (18.42%)  14/75 (18.67%) 
Neurotoxicity † 1  9/76 (11.84%)  6/75 (8.00%) 
Paraesthesia † 1  12/76 (15.79%)  9/75 (12.00%) 
Peripheral sensory neuropathy † 1  8/76 (10.53%)  13/75 (17.33%) 
Headache † 1  14/76 (18.42%)  15/75 (20.00%) 
Psychiatric disorders     
Anxiety † 1  3/76 (3.95%)  6/75 (8.00%) 
Insomnia † 1  15/76 (19.74%)  15/75 (20.00%) 
Renal and urinary disorders     
Dysuria † 1  1/76 (1.32%)  5/75 (6.67%) 
Reproductive system and breast disorders     
Amenorrhoea † 1  1/76 (1.32%)  5/75 (6.67%) 
Breast pain † 1  4/76 (5.26%)  2/75 (2.67%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  10/76 (13.16%)  8/75 (10.67%) 
Epistaxis † 1  12/76 (15.79%)  9/75 (12.00%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  40/76 (52.63%)  40/75 (53.33%) 
Dermatitis Acneiform † 1  4/76 (5.26%)  3/75 (4.00%) 
Dry skin † 1  5/76 (6.58%)  3/75 (4.00%) 
Erythema † 1  5/76 (6.58%)  4/75 (5.33%) 
Onycholysis † 1  5/76 (6.58%)  2/75 (2.67%) 
Pruritus † 1  6/76 (7.89%)  10/75 (13.33%) 
Rash † 1  19/76 (25.00%)  14/75 (18.67%) 
Rash maculo-papular † 1  4/76 (5.26%)  7/75 (9.33%) 
Vascular disorders     
Flushing † 1  7/76 (9.21%)  4/75 (5.33%) 
Hot flush † 1  6/76 (7.89%)  5/75 (6.67%) 
1
Term from vocabulary, MedDRA, version 20.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02301988    
Other Study ID Numbers: GO29505
2014-003029-16 ( EudraCT Number )
First Submitted: November 24, 2014
First Posted: November 26, 2014
Results First Submitted: July 26, 2018
Results First Posted: September 20, 2018
Last Update Posted: October 17, 2018