A Study of MetMAb Administered to Patients With Advanced Non-Small Cell Lung Cancer, in Combination With Tarceva (Erlotinib)

A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Activity of MetMAb, a Monovalent Antagonist Antibody to the Receptor Met, Administered to Patients With Advanced Non-Small Cell Lung Cancer, in Combination With Tarceva (Erlotinib)

This is a Phase II, double-blind, randomized, multicenter trial designed to preliminarily evaluate the activity and safety of treatment with MetMAb + erlotinib versus erlotinib + placebo in second- and third-line Non-Small Cell Lung Cancer (NSCLC). Up to 180 patients will be randomized in a 1:1 ratio to one of the two treatment arms.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib HCl; Drug: MetMAb; Drug: placebo (0.9 % saline)

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

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:

Patients must meet the following criteria for study entry:

• Histologically confirmed NSCLC
• Availability of a tumor specimen
• Recurrent or progressive disease following at least one chemo containing regimen for Stage IIIB/IV disease
• Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
• At least one measurable lesion on a pre-treatment 18-fluorodeoxyglcose-positron emission tomography (FDG-PET) scan that is also a target lesion on computed tomography (CT) according to RECIST

Exclusion Criteria:

• More than two prior treatments for Stage IIIB/IV
• More than 30 days of exposure to an investigational or marketed agent that can act by EGFR inhibition, or a known epidermal growth factor receptor (EGFR)-related toxicity resulting in dose modifications
• Chemotherapy, biologic therapy, radiotherapy or investigational drug within 28 days prior to randomization
• Untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis
• History of serious systemic disease within the past 6 months prior to randomization
• Uncontrolled diabetes
• Major surgical procedure or significant traumatic injury within 28 days prior to randomization
• Anticipation of need for a major surgical procedure during the course of the study
• Local palliative radiotherapy within 7 days prior to randomization or persistent adverse effects from radiotherapy that have not been resolved to Grade II or less prior to randomization
• Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MetMAb + Erlotinib; MetMab 15 mg/kg intravenous (IV) infusion every 3 weeks + Erlotinib 150 mg orally once daily until progression of disease or unacceptable toxicity.	Drug: Erlotinib HCl; Erlotinib 150 mg oral dose once daily.; Other Names: Tarceva; Drug: MetMAb; MetMab (a monovalent antagonist antibody to the receptor MET) 15 mg/kg in 250 CC 0.9% saline intravenous infusion every 3 weeks.
Placebo Comparator: Placebo + Erlotinib; Placebo IV infusion every 3 weeks + Erlotinib 150 mg orally daily until progression of disease or unacceptable toxicity.	Drug: Erlotinib HCl; Erlotinib 150 mg oral dose once daily.; Other Names: Tarceva; Drug: placebo (0.9 % saline); Placebo Intravenous infusion every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment).	Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months)
Progression-free Survival in Patients With Met Diagnostic-Positive Tumors	Progression-free survival (PFS) in participants with Met Diagnostic-Positive tumors as determined by immunohistochemistry. PFS was defined as the time from randomization to the first occurrence of progression or relapse (as per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by the site radiologist or investigator) or death on study from any cause (within 30 days of last treatment).	Time from randomization to the first occurrence of progression/relapse or death on study. (Up to 20 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response	Objective response (partial and complete response as determined using RECIST 1.0). Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions.	Start of treatment until disease progression/recurrence or death on study. (Up to 20 months)
Percentage of Participants With Objective Response in Patients With Met Diagnostic-Positive Tumors	Objective response (OR); partial and complete response as determined using RECIST 1.0 in patients with Met Diagnostic-Positive Tumors as determined by immunohistochemistry. Partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter. Complete response was defined as disappearance of all target lesions.	Start of treatment until disease progression/recurrence or death on study. (Up to 20 months)
Duration of Overall Response		Date of initial response until date of progression or death on study. (Up to 20 months)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Premal Patel, M.D., Ph.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 3, 2009

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 2, 2017
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Tarceva
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: OAM4558g