Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with taxane-based chemotherapy regimens utilized in patients with locally recurrent or metastatic breast cancer.

Official Title
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A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: GDC-0980
* Drug: bevacizumab
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally recurrent or metastatic breast cancer, not amenable to resection with curative intent For Arm C: Overexpression of HER2 Eastern Cooperative Oncology Group Performance Status of 0 or 1 Adequate hematologic and organ function Evaluable or measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors) Female patients of childbearing potential must use an acceptable method of contraception to prevent pregnancy and to continue its use for the duration of the study Exclusion Criteria: Prior anti-cancer therapy of more than two regimens of systemic cytotoxic chemotherapy for advanced or metastatic breast cancer Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment History of Type 1 or Type 2 diabetes requiring regular medication History of clinically significant cardiac or pulmonary dysfunction History of malabsorption syndrome or other condition that would interfere with enteral absorption Any condition requiring full-dose anticoagulants Leptomeningeal disease as a manifestation of cancer Active infection requiring IV antibiotics Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs, inhaled steroids, or the equivalent of <= 10 mg/day of prednisone Known clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis Known HIV infection Known untreated or active CNS metastases Pregnancy, lactation, or breastfeeding Major surgical procedure, open biopsy, or significant traumatic injury within a within a specified timeframe of the first dose of study treatment For Arm B: Uncontrolled hypertension, complication from hypertension, myocardial infarctions, unstable angina, vascular disease or stroke within a specified timeframe of the first dose of study treatment Evidence of bleeding diathesis or significant coagulopathy including hemoptysis within a specified timeframe of the first dose of study treatment History of abdominal conditions (e.g., fistula, perforation, obstruction) that would preclude use of bevacizumab Serious, non-healing wound, active ulcer, or untreated bone fracture Proteinuria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: GDC-0980<br>* Oral repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|
| Experimental: B<br> | Drug: GDC-0980<br>* Oral repeating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities (DLTs) |  | Through Day 22 | 
| Incidence, nature, and severity of adverse events |  | Through study completion, up to 1 year, or early discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of GDC-0980, paclitaxel and bevacizumab (including total exposure, maximum and minimum plasma concentration, time to maximum observed plasma concentration, plasma half-life) |  | Through Day 22 | 
| Duration of response |  | Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation | 
| Progression-free survival (PFS) |  | Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation | 
| Objective tumor response |  | Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation |