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
- Registration Number
- NCT01254526
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description A GDC-0980 - B GDC-0980 - A paclitaxel - B bevacizumab - B paclitaxel -
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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