Carboplatin, Ixabepilone, and Cetuximab in Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Untreated With Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving chemotherapy together with monoclonal antibodies may be a better way to block cancer growth. PURPOSE: This phase II trial is studying the side effects and how well giving carboplatin and ixabepilone together with cetuximab works in treating patients with stage III or stage IV non-small cell lung cancer previously untreated with chemotherapy.

Detailed Description
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OBJECTIVES: Primary To estimate the disease-control rate in patients with advanced chemotherapy-naive non-small cell lung cancer after 2 courses of carboplatin, ixabepilone, and cetuximab. Secondary To estimate the progression-free survival of patients treated with this regimen. To estimate the overall survival of patients treated with this regimen. To estimate the toxicity of this regimen in these patients. To determine the potential predictive marker of efficacy of ixabepilone and cetuximab. (exploratory) To investigate the prevalence of cetuximab IgE antibody, and the rate of cetuximab hypersensitivity reactions in patients without evidence of cetuximab IgE antibodies. OUTLINE: This is a multicenter study. Patients receive carboplatin IV over 30 minutes and ixabepilone IV over 3 hours on day 1 and cetuximab IV over 1-2 hours on days 1, 8 and 15. Treatment repeats every 21 days for up to 2-4 courses in the absence of disease progression or unacceptable toxicity. Treatment modifications may apply according to response. Tumor tissue and blood samples are collected for further analysis. After completion of study therapy, patients are followed periodically.

Official Title
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A Phase II Trial of Carboplatin, Ixabepilone and Cetuximab in Chemotherapy Naive Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cetuximab
* Drug: carboplatin
* Drug: ixabepilone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer Chemotherapy-naive Stage IIIB disease not amenable to surgery with pleural effusion, pericardial effusion, or not a candidate for chemoradiotherapy Stage IV disease Must have pathology block or unstained slides from initial or subsequent diagnosis Diagnosis made via a core biopsy (not a fine-needle aspirate) required Measurable disease as defined by RECIST guidelines For patient who received prior radiotherapy, evaluable disease must be outside of the radiation field, or have new lesions that developed within the radiation field Brain metastasis allowed provided it has been treated and determined to be controlled by the treating physician No IgE cetuximab antibody PATIENT CHARACTERISTICS: ECOG performance status 0-1 ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL Creatinine < 2.0 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastasis) Bilirubin ≤ 1.5 times ULN Prior malignancy allowed provided the treating physician determines that the patient's life expectancy is best defined by diagnosis of non-small cell lung cancer (NSCLC) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No peripheral neuropathy ≥ grade 2 by NCI CTCAE v. 3.0 No prior severe allergic reaction to any of the following: Carboplatin Taxane therapy Monoclonal antibody Hypersensitivity (NCI CTCAE grade3-4) to a drug formulated in Cremophor® EL (polyoxyethylated castor oil) No active or uncontrolled infection No significant history of uncontrolled cardiac disease including, but not limited to, any of the following: Uncontrolled hypertension Unstable angina Myocardial infarction within the past 6 months Uncontrolled congestive heart failure Cardiomyopathy with decreased ejection fraction No underlying interstitial lung disease PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 1 week since prior and no concurrent therapeutic radiotherapy Palliative radiotherapy for painful bone lesions allowed At least 6 months since prior adjuvant chemotherapy No investigational agent(s) within the past 30 days Not requiring concurrent treatment with any of the following: Ketoconazole Itraconazole Ritonavir Amprenavir Indinavir Nelfinavir Delavirdine Voriconazole No other concurrent chemotherapy or cetuximab

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cetuximab|400 mg/m2 Cycle 1 day 1 only over 120 minutes 250 mg/m2 Cycle 1 days 8,15 AND on all other cycles days 1,8,15 over 60 minutes|
|Drug: carboplatin|AUC=6 Day 1 of treatment over 30 minutes every 21 days|
|Drug: ixabepilone|30 mg/m2 , Day 1 over 3 hours every 21 days|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-control rate after 2 courses of carboplatin, cetuximab, and ixabepilone | Disease control rate will be defined as patients experiencing a complete or partial response or stable disease (radiographic response) measured by RECIST criteria. | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Radigoraphic response of measurable disease will be assessed using RECIST critera | 2 years | 
| Overall survival | Radigoraphic response of measurable disease will be assessed using RECIST criteria | 4 years | 
| Number of subjects experiencing adverse events | Adverse events will be assessed (graded) using CTCAE criteria | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer