A Phase Ib, Open Label, Dose Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors
Inclusion Criteria:
- Histologically or cytologically documented locally advanced or metastatic solid
tumors for which established therapy is ineffective, not tolerable, or does not exist
- Patients with histologically or cytologically documented locally advanced or
metastatic breast cancer who have received at least one prior chemotherapy-based
regimen for incurable disease (Arm A)
- Patients with histologically or cytologically documented locally advanced or
metastatic CRC who have not received prior oxaliplatin-based therapy within 1 year of
initiation of study treatment. (Arm B)
Exclusion Criteria:
- Prior anti-cancer therapy that fulfills the following criteria: a total of more than
six courses of an alkylating agent, a total of more than four courses of
carboplatin-containing chemotherapy regimens, and a total of more than two courses of
nitrosoureas or mitomycin C, high-dose chemotherapy requiring stem-cell support, and
irradiation to >= 25% of bone marrow-bearing areas
- Current dyspnea at rest because of complications of advanced malignancy or other
disease requiring continuous oxygen therapy
- Known deficiency of dihydropyrimidine dehydrogenase (DPD)
- Bisphosphonate therapy for symptomatic hypercalcemia
- Known untreated or active central nervous system (CNS) metastases
- Pregnancy, lactation, or breastfeeding
For Arm B:
- Inadequately controlled hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History of myocardial infarction or unstable angina within 6 months prior to the
first dose of study treatment
- History of stroke or transient ischemic attacks within 6 months prior to the first
dose of study treatment
- Significant vascular disease within 6 months prior to the first dose of study
treatment
- History of hemoptysis within 1 month prior to the first dose of study treatment
- Patients with one or more pulmonary tumor masses with evidence of cavitation
- Evidence of bleeding diathesis or significant coagulopathy
- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to the first dose of study treatment
- History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6
months prior to the first dose of study treatment
- Clinical signs or symptoms of GI obstruction or requirement for parenteral hydration,
parenteral nutrition, or tube feeding
- Evidence of abdominal free air not explained by paracentesis or recent surgical
procedure
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- The presence of an ulcerating breast cancer tumor will not render a patient
ineligible
- Proteinuria