A Study of Paclitaxel With GDC-0941 Versus Paclitaxel With Placebo in Participants With Locally Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This multicenter, randomized, single-blind, placebo-controlled, two arm study will evaluate the efficacy and safety of paclitaxel with GDC-0941 versus paclitaxel with placebo in participants with locally recurrent or metastatic breast cancer.

Official Title
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A Phase II, Randomized Study of Paclitaxel With GDC-0941 Versus Paclitaxel With Placebo in Patients With Locally Recurrent or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: GDC-0941
* Drug: Placebo
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease Human epidermal growth factor receptor 2 (HER2)-negative and hormone receptor (HR) (estrogen receptor and/or progesterone receptor)-positive disease as defined by local guidelines Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematologic and end organ function Women of childbearing potential must agree to remain abstinent or to use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 30 days after the last dose of study treatment or 6 months after discontinuation of paclitaxel, whichever is longer Exclusion Criteria: Prior non-capecitabine chemotherapy for locally recurrent or metastatic disease Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor for advanced or metastatic breast cancer History of intolerance to a taxane-containing therapy History of clinically significant cardiac or pulmonary dysfunction History of malabsorption syndrome or other condition that would interfere with enteral absorption Clinically significant history of liver disease Active autoimmune disease or active inflammatory disease Immunocompromised status due to current known active infection with human immunodeficiency virus (HIV) or due to the use of immunosuppressive therapies for other conditions Need for current chronic corticosteroid therapy Pregnant, lactating, or breastfeeding women Current severe, uncontrolled systemic disease Known untreated or active central nervous system (CNS) metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Paclitaxel, GDC-0941<br>Participants will receive GDC-091 260 milligrams (mg) orally in repeated rounds of once daily (QD) dosing for 5 consecutive days followed by 2 consecutive days during which GDC-0941 will not be administered (5/7-day schedule). This 5/7-day schedule will be repeated weekly in each 28-day cycle until disease progression or intolerable toxicity. Participants will receive 90 milligrams per square meter (mg/m^2) intravenously (IV) weekly for 3 out of 4 weeks in every 28-day cycle. | Drug: GDC-0941<br>* GDC-0941 will be administered QD orally for 5 consecutive days each week.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered IV weekly for 3 out of 4 weeks in every 28-day cycle.<br>|
| Placebo Comparator: B: Paclitaxel, Placebo<br>Participants will receive placebo matching to GDC-0941 on the 5/7-day schedule along with 90 mg/m^2 IV weekly for 3 out of 4 weeks in every 28-day cycle. | Drug: Placebo<br>* Placebo matching to GDC-0941<br>Drug: Paclitaxel<br>* Paclitaxel will be administered IV weekly for 3 out of 4 weeks in every 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Assessed as per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) |  | From the time of randomization until disease progression or death from any cause (up to approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | From randomization up to approximately 3 years | 
| Percentage of Participants With Objective Tumor Response Assessed as per Modified RECIST v1.1 |  | From first observation of an objective tumor response until disease progression (up to approximately 3 years) | 
| Percentage of Participants Acheiving Clinical Benefit (Partial Response, Complete Response or Stable Disease Lasting for at Least 6 Months) Assessed as per Modified RECIST v1.1 |  | From randomization until disease progression (up to approximately 3 years) | 
| Duration of Confirmed Objective Response Assessed as per Modified RECIST v1.1 |  | From first observation of an objective tumor response until disease progression (up to approximately 3 years) | 
| Population Pharmacokinetics (PK) for GDC-0941 |  | Day 8 of Cycle 1 and Day 1 of Cycle 6 (cycle length=28 days) | 
| Population PK for Paclitaxel |  | Day 1 of Cycle 1 (cycle length=28 days) |