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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of MEGF0444A, a Human IgG1 Antibody, in Combination With Bevacizumab and Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: MEGF0444A
* Drug: bevacizumab
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: MEGF0444A<br>* Intravenous escalating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>|
| Experimental: B<br> | Drug: MEGF0444A<br>* Intravenous escalating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities (DLTs) |  | Days 1 to 28 of Cycle 1 | 
| Incidence, nature, and severity of adverse events |  | Until 90 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters including total exposure, minimum and maximum serum concentration, clearance, and volume of distribution |  | Following administration of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor