A Study to Determine Whether EGFR Status by FISH Can Predict Results in Non Small Cell Lung Cancer (NSCLC) Patients Treated With Cetuximab, Carboplatin and Paclitaxel

Study Overview
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Brief Summary
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The purpose of this study is to determine if EGFR status (positive or negative) by FISH can predict response to cetuximab therapy in NSCLC patients treated with carboplatin and paclitaxel

Official Title
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A Randomized Phase II Trial to Assess the Predictive Value of Increased EGFR Copy Number by FISH in Patients With Advanced / Metastatic NSCLC Treated With Cetuximab and Carboplatin / Paclitaxel

Conditions
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Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who present with Stage IV, Stage IIIB NSCLC or recurrent disease following radiation therapy or surgical resection No prior chemotherapy or anti-EGFR targeted therapy Sufficient tumor material for FISH testing Measurable disease (RECIST) ECOG performance status 0 or 1 Exclusion Criteria: Symptomatic or uncontrolled CNS metastases Inadequate hematologic function defined as ANC < 1,500/mm3, platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dl Inadequate hepatic function defined as total bilirubin > 1.25 x ULN, AST level > 1.5 x ULN, or alkaline phosphatase > 5.0 x ULN Inadequate renal function defined by a serum creatinine level > 1.5 x ULN

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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 FISH (+)<br> | Drug: Cetuximab<br>* Vial, Intravenous, 400 mg/m² week 1 then 250 mg/m², Weekly, Until PD/Toxicity/Pt-PI Decision<br>* Other names: BMS-564717;Drug: Paclitaxel<br>* Vial, Intravenous, 225 mg/m2, Every 3 weeks, 6 cycles maximum<br>Drug: Carboplatin<br>* Vial, Intravenous, AUC = 6.0, Every 3 weeks, 6 cycles maximum<br>|
| Active Comparator: B1 FISH (+)<br> | Drug: Paclitaxel<br>* Vial, Intravenous, 225 mg/m2, Every 3 weeks, 6 cycles maximum<br>Drug: Carboplatin<br>* Vial, Intravenous, AUC = 6.0, Every 3 weeks, 6 cycles maximum<br>|
| Experimental: A2 FISH (-)<br> | Drug: Cetuximab<br>* Vial, Intravenous, 400 mg/m² week 1 then 250 mg/m², Weekly, Until PD/Toxicity/Pt-PI Decision<br>* Other names: BMS-564717;Drug: Paclitaxel<br>* Vial, Intravenous, 225 mg/m2, Every 3 weeks, 6 cycles maximum<br>Drug: Carboplatin<br>* Vial, Intravenous, AUC = 6.0, Every 3 weeks, 6 cycles maximum<br>|
| Active Comparator: B2 FISH (-)<br> | Drug: Paclitaxel<br>* Vial, Intravenous, 225 mg/m2, Every 3 weeks, 6 cycles maximum<br>Drug: Carboplatin<br>* Vial, Intravenous, AUC = 6.0, Every 3 weeks, 6 cycles maximum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) will be compared for FISH positive subjects (subset) receiving paclitaxel / carboplatin +/- cetuximab |  | Every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  | Every 6 weeks | 
| Disease control |  | Every 6 weeks | 
| Overall survival (OS) |  | Every 4 months after subject off-treatment until 1 year after LPLT | 
| Duration of Response |  | Every 6 weeks | 
| Safety & exploratory biomarker analysis |  | Every 3 weeks |