This is a randomized, double-blind, placebo-controlled, multicenter, pre-operative Phase II study designed to estimate the efficacy of ipatasertib combined with paclitaxel chemotherapy versus placebo combined with paclitaxel chemotherapy in women with Stage Ia - IIIa triple-negative breast adenocarcinoma. The anticipated time on study treatment is 12 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
151
Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.
Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m\^2) as IV infusion QW for 3 cycles.
Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.
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)
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)
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)
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)
Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)
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)
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)
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.
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Arizona Oncology Associates, PC-CASA
Tucson, Arizona, United States
Sansum Medical Clinic, Inc.
Santa Barbara, California, United States
Rocky Mountain Cancer Center - Lakewood (West)
Lakewood, Colorado, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Mass General/North Shore Cancer
Danvers, Massachusetts, United States
Nebraska Cancer Specialists; Oncology Hematology West, PC
Omaha, Nebraska, United States
Carolinas Healthcare System
Charlotte, North Carolina, United States
Northwest Cancer Specialists - Portland (NE Hoyt St)
Portland, Oregon, United States
Roper Bon Secours St. Francis Cancer Center
Charleston, South Carolina, United States
Texas Oncology
Austin, Texas, United States
...and 32 more locations
Time frame: Surgery visit (at approximately Weeks 14 to 19)
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)
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])
Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)
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])
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+])
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)
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+)
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)
Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype
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)
Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors
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)
Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors
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)
Percentage of Participants With Adverse Events
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
Plasma Concentrations of Ipatasertib on Day 1 and Day 8
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)
Minimum Observed Plasma Concentration (Cmin) of Ipatasertib
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)