Combination Chemotherapy With or Without Tirapazamine in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin plus paclitaxel with or without tirapazamine in treating patients who have stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the effects of paclitaxel and carboplatin with or without tirapazamine on progression-free survival and overall survival in patients with stage IV and selected stage IIIB non-small cell lung cancer. Compare response rates in patients treated with these regimens. Compare the toxic effects of these regimens in these patients. OUTLINE: This is a randomized study. Patients are stratified according to weight loss (less than 5% vs 5% or more), stage of disease (IIIB vs IV), and lactate dehydrogenase level (normal vs abnormal). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive tirapazamine IV over 2 hours followed by paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Arm II: Patients receive paclitaxel and carboplatin as in arm I. Treatment continues every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for one year, and then every 6 months for 2 years, or until death. PROJECTED ACCRUAL: Approximately 500 patients (250 per arm) will be accrued for this study within 20 months.

Official Title
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Randomized Phase III Trial Of Carboplatin And Paclitaxel Plus Tirapazamine Versus Carboplatin And Paclitaxel In Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: tirapazamine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven newly diagnosed advanced primary non-small cell lung cancer (NSCLC), including the following cellular types: Adenocarcinoma Large cell carcinoma Squamous cell carcinoma Unspecified carcinoma OR Recurrent disease after prior surgery and/or radiotherapy Stage IIIB disease T4 lesion due to malignant pleural effusion OR Stage IV disease Any T, any N, M1 (distant metastasis, including lesions in multiple lobes of the ipsilateral lung) Measurable or evaluable disease Pleural effusions, ascites, and laboratory parameters not considered as only evidence of disease Must be outside prior radiated field or area of prior surgical resection or new lesion must be present No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT or SGPT no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than ULN Creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception No peripheral neuropathy (motor or sensory) of grade 2 or greater No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I/II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for NSCLC Chemotherapy: No prior systemic chemotherapy for NSCLC Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics At least 2 weeks since prior thoracic or other major surgery and recovered

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: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Drug: tirapazamine|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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recurrent non-small cell lung cancer, squamous cell lung cancer, large cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung