Chemotherapy, Tirapazamine, and Radiation Therapy in Treating Patients With 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. Radiation therapy uses high-energy x-rays to damage tumor cells. Tirapazamine may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and tirapazamine may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining chemotherapy with tirapazamine and radiation therapy in treating patients who have stage II or stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of tirapazamine when administered with paclitaxel, carboplatin, and concurrent radiotherapy in patients with stage IIB-IIIB non-small cell lung cancer. Determine, preliminarily, the response rate and survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, dose-escalation study of tirapazamine. Patients receive induction chemotherapy comprising tirapazamine IV over 2 hours and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36 and paclitaxel IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39. Beginning on day 1, patients undergo radiotherapy once daily 5 days a week for 6.5 weeks. Beginning 4-5 weeks after completion of radiotherapy, patients with stable or responding disease receive consolidation chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 1 and 22. Cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Official Title
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A Phase I Study Of Tirapazamine (NSC 130181) Paclitaxel And Carboplatin With Concurrent Radiation Followed By Tirapazamine/Paclitaxel/Carboplatin Consolidation For Stage III Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: tirapazamine
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed primary bronchogenic non-small cell lung cancer Adenocarcinoma Large cell carcinoma Squamous cell carcinoma Stage IIIA or IIIB disease (T1-4, N2-3) Mediastinal lymph nodes at least 2 cm in diameter by radiography sufficient to stage N2-3 (must be node positive [cytologically or histologically confirmed] if largest mediastinal node is less than 2 cm in diameter) OR Selected stage IIB disease (T3, N0 or T3, N1 with a medical condition that precludes surgery) No malignant pleural effusion Measurable or evaluable disease by chest x-ray or CT scan No metastatic disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 OR ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm^3 Platelet count normal Hepatic: Not specified Renal: Creatinine clearance at least 60 mL/min Cardiovascular: No uncontrolled congestive heart failure No unstable angina No unstable cardiac arrhythmias Pulmonary: FEV_1 at least 1.0 L Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No clinically significant hearing loss PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for lung cancer Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for lung cancer Surgery: See Disease Characteristics

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


Arms and Interventions

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