A Study of the Safety and Pharmacology of MEGF0444A in Combination With Bevacizumab With or Without Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors

• Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: Days 1 to 28 of Cycle 1 ] [ Designated as safety issue: No ]
• Incidence, nature, and severity of adverse events [ Time Frame: Until 90 days after last dose of study treatment ] [ Designated as safety issue: No ]

This is a Phase Ib, open-label, dose-escalation study of MEGF0444A in combination with bevacizumab, and in combination with bevacizumab and paclitaxel as therapy for locally advanced or metastatic solid tumors.

• Drug: bevacizumab
  Intravenous repeating dose
• Drug: MEGF0444A
  Intravenous escalating dose
• Drug: paclitaxel
  Intravenous repeating dose

• Experimental: A
  Interventions:

  • Drug: bevacizumab
  • Drug: MEGF0444A
• Experimental: B
  Interventions:

  • Drug: bevacizumab
  • Drug: MEGF0444A
  • Drug: paclitaxel

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