Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody, Cetuximab, in Combination With Gemcitabine/Carboplatin in Patients With Stage IV Lung Cancer

Study Overview
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Brief Summary
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The objective is to evaluate the toxicity profile, response rate, and time to progression of Cetuximab administered in combination with either Carboplatin + Gemcitabine in patients with advanced non-small cell lung cancer with positive EGFr expression.

Detailed Description
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The primary objective of this study is to evaluate the safety profile of Cetuximab when used in combination with gemcitabine and carboplatin in patients with EGFr positive, chemotherapy-naive, stage IV non-small cell lung cancer (NSCLC). Also, the study will determine the response rate in patients with EGFr positive chemotherapy-naive, stage IV non-small cell lung cancer (NSCLC) treated with Cetuximab in combination with gemcitabine and carboplatin as well as determine the time to progression in patients with EGFr positive chemotherapy-naive, stage IV NSCLC treated with Cetuximab in combination with gemcitabine and carboplatin.

Official Title
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Phase Ib, IIa Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody, Cetuximab, in Combination With Gemcitabine/Carboplatin in Patients With Chemotherapy-Naive Stage IV Non-Small Cell Lung Cancer

Conditions
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Stage IV Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Cetuximab in combination with Carboplatin/Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of histologically/cytologically confirmed advanced non- small cell lung cancer (NSCLC). Have uni-dimensionally measurable and/or evaluable advanced NSCLC. Have Stage IV or recurrent disease following radiation therapy. Have ECOG performance status of 0-1 or Karnofsky performance status of 80- 100 at study entry. Have given signed informed consent. Be at least 18 years of age. Have ANC greater than or equal to 1,500/mm3, platelets greater than or equal to 100,000/mm3, WBC greater than or equal to 3,000 mm3, and hemoglobin greater than or equal to 9 g/dL. Have total bilirubin less than or equal to 1.5 x upper limits of normal, Alk Phos, AST and ALT less than or equal to 2.5 x upper limits of normal. Have serum creatinine less than or equal to 1.5 mg/dL, or calculated creatinine clearance greater than or equal to 60 cc/minute. Be disease free from a previously treated malignancy for more than three years. Patients with a history or a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix will not be excluded. Agree to use effective contraception if procreative potential exists. Must have positive EGFr expression (tumor tissue) by immunohistochemical assay. Exclusion Criteria: Have received prior murine monoclonal antibody or Cetuximab therapy. Have disease amenable to curative surgery. Have received prior chemotherapy. Have received radiation therapy within 3 weeks prior to the first infusion of Cetuximab. Have a history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities, in the judgment of the PI. Have uncontrolled seizure disorder, active neurological disease, or Grade 2 or higher neuropathy. Be pregnant or breast-feeding. Have received any investigational agent(s) within 1 month of study entry.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab in combination with Carboplatin/Gemcitabine<br>Approximately 30 patients with advanced NSCLC will be enrolled. Patients will receive 3-week cycles of Cetuximab in combination with Carboplatin/Gemcitabine. | Drug: Cetuximab in combination with Carboplatin/Gemcitabine<br>* A loading dose of Cetuximab (400 mg/m2 IV over 120 minutes) will be administered 1 week prior to chemotherapy. Thereafter, Cetuximab will be infused weekly at maintenance doses of 250 mg/m2 (over 60 minutes). On the first day of each new cycle of therapy, Carboplatin will be infused with Gemcitabine (Days 1 and 8). Patients will be evaluated for a tumor response following every two cycles of therapy. In the absence of progressive disease, patients may continue to receive additional therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the tumor response of cetuximab in combination with gemcitabine and carboplatin in patients with EGFr positive, chemotherapy-naive, Stage IV non-small cell lung cancer. |  | 3-week cycles with evaluation after every 2 cycles until disease progression or unacceptable toxicity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the response rate and time to disease progression |  | 3-week cycles with evaluation after every 2 cycles until disease progression or unacceptable toxicity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFr, cetuximab, gemcitabine, carboplatin, NSCLC