Erlotinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib together with paclitaxel and carboplatin may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different doses of erlotinib when given together with paclitaxel and carboplatin to compare how well they work in treating patients with stage III, stage IV, or recurrent non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the major objective response (complete and partial response) rates in patients with stage IIIB or IV or recurrent non-small cell lung cancer treated with high- versus low-dose erlotinib hydrochloride combined with paclitaxel and carboplatin. Compare the duration of response, time to progression, and survival of patients treated with these regimens. Characterize and compare the toxicities of these regimens. Determine the recommended phase III dose of erlotinib hydrochloride. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral high-dose erlotinib hydrochloride on days 1 and 2. Patients also receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 3. Arm II: Patients receive oral low-dose erlotinib hydrochloride, paclitaxel, and carboplatin as in arm I. In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

Official Title
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A Randomized Phase II Trial Comparing Two Doses of Pulsed Erlotinib Prechemotherapy (PEP-C) in Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: erlotinib hydrochloride
* Drug: Paclitaxel
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed non-small cell lung cancer Stage IIIB or IV or recurrent disease Measurable or evaluable indicator lesions Must have smoked ≥ 100 cigarettes in his/her lifetime PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% WBC ≥ 4,000/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min Bilirubin ≤ 1.0 mg/dL AST ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 1 week after completion of study treatment No gastrointestinal tract disease or inability to take oral medication No prior malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No other active medical problems, including severe infection, unstable angina, or myocardial infarction within the past 6 months No poorly controlled hypertension or severe malnutrition No New York Heart Association class III or IV congestive heart failure or serious cardiac arrhythmia requiring medication except chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) PRIOR CONCURRENT THERAPY: At least 3 weeks since prior radiotherapy to major bone marrow-containing sites No prior chemotherapy for advanced non-small cell lung cancer No prior agents directed at the epidermal growth factor receptor (EGFR)/HER axis (e.g., gefitinib, cetuximab, or trastuzumab [Herceptin®]) No prior surgical procedure resulting in abnormal absorption of oral medications No concurrent surgical resection, palliative radiotherapy, or hormonal therapy No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150 PRE<br>Erlotinib 150mg on days 1 and 2 of a 21 day cycle and Carboplatin AUC6 and Paclitaxel 200 mg/m2 | Drug: Carboplatin<br> <br> * Other names: Carboplatin AUC6;Drug: erlotinib hydrochloride<br>* 150mg<br>* Other names: Erlotinib;Drug: Paclitaxel<br>* 200mg/m2<br>|
| Experimental: 1,500 PRE<br>Erlotinib 1500mg on Days 1 and 2 of a 21 day cycle and Carboplatin AUC6 and Paclitaxel 200mg/m2 | Drug: Carboplatin<br> <br> * Other names: Carboplatin AUC6;Drug: Paclitaxel<br>* 200mg/m2<br>Drug: erlotinib hydrochloride<br>* 1500mg<br>* Other names: Erlotinib;|
| Experimental: 1,500 POST<br>Carboplatin AUC6, Paclitaxel 200 mg/m2 followed by Erlotinib 1500mg days 2 and 3. | Drug: Carboplatin<br> <br> * Other names: Carboplatin AUC6;Drug: Paclitaxel<br>* 200mg/m2<br>Drug: erlotinib hydrochloride<br>* 1500mg<br>* Other names: Erlotinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Percentage of patients who experienced complete or partial response as defined by RECIST | after 6 cycles of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Median number of months until disease progression | after cycle 6 of chemotherapy | 

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