Cetuximab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Unresectable Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with paclitaxel, carboplatin, and radiation therapy works in treating patients with unresectable stage IIIA or stage IIIB non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of cetuximab when administered concurrently with paclitaxel, carboplatin, and radiotherapy, in terms of safety and compliance, in patients with unresectable stage IIIA or IIIB non-small cell lung cancer. Secondary Determine the response rate (complete and partial) in patients treated with this regimen. Determine the overall survival (1- and 2-year survival rate and median survival) of patients treated with this regimen. Determine the time to disease progression (at 1 and 2 years) in patients treated with this regimen. Correlate epidermal growth factor receptor expression with the toxicity of this regimen and response, overall survival, and progression in these patients. OUTLINE: This is a multicenter study. Cetuximab loading dose (week 1): Patients receive a loading dose of cetuximab IV over 2 hours on day 1. Concurrent cetuximab and chemoradiotherapy (weeks 2-8): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50-53. Consolidation therapy (weeks 9-17): Patients receive cetuximab IV over 1 hour on days 57, 64, 71, 78, 85, 92, 99, 106, and 113. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 78 and 99. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 30 days, every 3 months for 2 years, every 4 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 1 year.

Official Title
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A Phase II Study Of Cetuximab (C225) In Combination With Chemoradiation In Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: carboplatin
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following subtypes: Squamous cell carcinoma Adenocarcinoma (including bronchoalveolar cell) Large cell anaplastic carcinoma (including giant and clear cell carcinomas) Poorly differentiated/not otherwise specified NSCLC Stage IIIA (T1-2, N2, M0 or T3, N1-2, M0) or IIIB (T4, any N, M0 or any T, N2-3, M0) If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least 1 of the nodes must be cytologically or histologically positive Unresectable disease No totally resected tumors Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiation boost field and the boost volume is limited to < 50% of the ipsilateral lung volume Measurable disease Transudate, cytologically negative, non-bloody pleural effusions allowed provided the tumor can be encompassed within a reasonable field of radiotherapy Pleural effusions seen on a chest CT scan are allowed provided they are not visible on a chest x-ray and are too small to tap No asymptomatic or symptomatic brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL (transfusion independent) Hepatic Bilirubin ≤ 1.5 mg/dL SGOT (serum glutamic oxaloacetic transaminase) or SGPT (serum glutamate pyruvate transaminase) ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 2.0 mg/dL Cardiovascular No significant history of cardiac disease No uncontrolled hypertension No unstable angina No uncompensated congestive heart failure No myocardial infarction within the past year No cardiac ventricular arrhythmias requiring medication LVEF (left ventricular ejection fraction) normal by MUGA (multi-gated acquisition) scan or echocardiogram Pulmonary No history of interstitial pneumonitis No history of severe chronic obstructive pulmonary disease requiring 3 or more hospitalizations within the past year FEV_1 ≥ 1,200 cc No active pulmonary infection unresponsive to conventional antibiotics Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 weeks after study therapy Glucose ≤ 2 times ULN No more than 5% weight loss within the past 3 months No known allergy to murine proteins or Cremophor EL No neuropathy grade 2 or greater No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ cancers PRIOR CONCURRENT THERAPY: Biologic therapy No prior drugs that target the epidermal growth factor receptor pathway No prior chimerized monoclonal antibody therapy No other concurrent immunotherapy No concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] and sargramostim [GM-CSF]) Concurrent epoetin alfa allowed Chemotherapy No prior systemic chemotherapy No other concurrent chemotherapy Endocrine therapy No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics Radiotherapy No prior thoracic or neck radiotherapy No concurrent intensity-modulated radiotherapy Surgery Recovered from prior exploratory thoracotomy No prior surgical resection of the present cancer Other More than 30 days since prior participation in another clinical trial No concurrent participation in another clinical trial No other concurrent anticancer therapy No amifostine during or for 3 months after study radiotherapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer