Lung-MAP: Rilotumumab and Erlotinib Hydrochloride or Erlotinib Hydrochloride Alone as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

Study Overview
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Brief Summary
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This randomized phase II/III compares rilotumumab when given together with erlotinib hydrochloride against erlotinib hydrochloride alone in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the met proto-oncogene (MET)/hepatocyte growth factor (HGF) biomarker. HGF can interact with MET and can cause tumor cells to grow more quickly. Rilotumumab may decrease the activity of HGF and may be able to shrink tumors. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving rilotumumab with erlotinib hydrochloride works better than erlotinib hydrochloride alone (standard treatment) in treating squamous cell lung cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate if there is sufficient evidence to continue to the phase III component of S1400E by comparing investigator-assessed progression-free survival (IA-PFS) between rilotumumab plus erlotinib versus erlotinib in patients registered to S1400E. (Phase II) II. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS between patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase III) III. To compare overall survival (OS) in patients randomized to rilotumumab plus erlotinib versus erlotinib. (Phase III) SECONDARY OBJECTIVES: I. To compare response rates (confirmed and unconfirmed, complete and partial responses) among patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase II) II. To evaluate the frequency and severity of toxicities associated with rilotumumab plus erlotinib versus erlotinib. (Phase II) III. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase III) IV. To evaluate the frequency and severity of toxicities associated with rilotumumab plus erlotinib versus erlotinib. (Phase III) TERTIARY OBJECTIVES: I. To evaluate the treatment arm randomization acceptance rate within each treatment arm of S1400E defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. II. To identify additional predictive or prognostic tumor/blood biomarkers beyond the chosen biomarker. III. To identify potential resistance biomarkers at disease progression. IV. To establish a tissue/blood repository from patients with refractory squamous cell cancer. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive rilotumumab intravenously (IV) over 60-120 minutes on day 1 and erlotinib hydrochloride orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, all patients will be followed until death or 3 years after sub-study registration, whichever occurs first.

Official Title
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A Phase II/III Randomized Study of Rilotumumab Plus Erlotinib Versus Erlotinib as Second Line Therapy for C-Met Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

Conditions
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MET Positive, Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma AJCC v7

Intervention / Treatment
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* Drug: Erlotinib Hydrochloride
* Other: Laboratory Biomarker Analysis
* Biological: Rilotumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) Patients must be assigned to S1400E; S1400E biomarker eligibility defined as C-MET positive is defined as follows: Analyte: C-MET Assay: Immunohistochemistry (IHC) Eligible definition: IHC positive based on Dako MET-IHC pharm DX kit If randomized to arm I rilotumumab plus erlotinib, patients must be willing to provide blood specimens for anti-rilotumumab anti-body testing Patients must not have peripheral edema > grade 1 at the time of sub-study registration Patients must not have received prior treatment with MET pathway, inhibitors or EGFR inhibitors (e.g., erlotinib) Patients must have total bilirubin =< 1.5 x institutional upper limits of normal (IULN) within 28 days prior to sub-study registration Patients must not have abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjorgren?s syndrome), congenital abnormality (e.g., Fuch?s dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or abnormal corneal sensitivity test (Schirmer test or similar tear production test) Patients must not be taking, nor plan to take while on protocol treatment and for 14 days post the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate CYP3A4 substrates

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (rilotumumab, erlotinib)<br>Patients receive rilotumumab IV over 60-120 minutes on day 1 and erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AND INTERVENTION 11/25/2014) | Drug: Erlotinib Hydrochloride<br>* Given PO<br>* Other names: Tarceva;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: Rilotumumab<br>* Given IV<br>* Other names: Fully Human Anti-HGF Monoclonal Antibody AMG 102;|
| Active Comparator: Arm II (erlotinib)<br>Patients receive erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AND INTERVENTION 11/25/2014) | Drug: Erlotinib Hydrochloride<br>* Given PO<br>* Other names: Tarceva;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed Progression-free Survival Between Arms | A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual | 
| Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial) Between Arms |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Toxicities Associated With Investigational Therapy Versus Standard of Care |  | Up to 3 years |