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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib HCl
* Drug: MetMAb
* Drug: placebo (0.9 % saline)


Participation Criteria
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Eligibility Criteria
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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

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: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tarceva, Lung Cancer, NSCLC