Breast Cancer
Conditions
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.
Interventions
DRUGGDC-0980
Oral repeating dose
DRUGbevacizumab
Intravenous repeating dose
DRUGpaclitaxel
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Belgium, United States
Outcome results
None listed