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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: bevacizumab; Drug: paclitaxel; Drug: MEGF0444A

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • California
    • San Francisco, California, United States, 94115
    • Santa Monica, California, United States, 90404
  • Florida
    • Tampa, Florida, United States, 33612
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: bevacizumab; Intravenous repeating dose; Drug: MEGF0444A; Intravenous escalating dose
Experimental: B	Drug: bevacizumab; Intravenous repeating dose; Drug: paclitaxel; Intravenous repeating dose; Drug: MEGF0444A; Intravenous escalating dose

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Solid Tumor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: MEF4797g; GO01328 (Other Identifier: Hoffmann-La Roche)