A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of MEGF0444A, a Humanized IgG1 Antibody, in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors
Inclusion Criteria:
- Histologically or cytologically documented, incurable, or metastatic solid malignancy
that has progressed on or failed to respond to regimens or therapies known to provide
clinical benefit
Specific to Arm A:
- For patients undergoing optional or mandatory exploratory MRI, at least one tumor
lesion that represents a liver, fixed peritoneal, neck, extremity, or pelvic lesion
measuring >/= 3 to 10 cm (for liver lesions) or >= 2 to 10 cm (for all other lesion
locations) to be used for MRI
Specific to Arm B:
- Maximum of two prior chemotherapy regimens for metastatic disease
Exclusion Criteria:
- Anti-cancer therapy within 3 weeks prior to initiation of study treatment
- Patients who had to discontinue prior bevacizumab therapy due to intolerable toxicity
- Leptomeningeal disease
- Active infection or autoimmune disease
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, or cirrhosis
- Known primary central nervous system (CNS) malignancy or untreated or active CNS
metastases
- Inadequately controlled hypertension; history of hypertensive crisis or
encephalopathy; congestive heart failure (New York Heart Association Class II or
greater); history of myocardial infarction or unstable angina within 6 months prior
to initiation of study treatment
- History of hemoptysis; evidence of bleeding diathesis or significant coagulopathy
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to initiation of study treatment
- Serious, non-healing wound, active gastrointestinal ulcer, or untreated bone fracture
Specific to Arm B:
- Known significant hypersensitivity to paclitaxel or other drugs using the vehicle
cremophor
- Previous intolerance to paclitaxel
- Grade >= 2 sensory neuropathy