S0004: Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Limited-stage 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. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the feasibility of tirapazamine, cisplatin, and etoposide concurrently with radiotherapy in patients with limited stage small cell lung cancer. Determine the toxicities of this treatment regimen in these patients. Determine the response rate in these patients treated with this regimen. OUTLINE: Patients are assigned to one of two induction therapy arms. Arm I: Patients receive induction chemotherapy consisting of low-dose tirapazamine IV over 1 hour and cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients also undergo radiotherapy concurrently with chemotherapy 5 consecutive days a week for 7 weeks beginning on day 1. Arm II: Patients receive induction chemotherapy consisting of high-dose tirapazamine, cisplatin, etoposide, and radiotherapy as in arm I. Patients with stable or responding disease then receive consolidation therapy consisting of tirapazamine IV over 1 hour and cisplatin IV over 1 hour on day 1 of weeks 11 and 14 and etoposide IV over 1 hour on days 1-3 of weeks 11 and 14. Patients are followed every 2 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 50 patients (25 per arm) will be accrued for this study.

Official Title
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A Phase I Study Of Tirapazamine/Cisplatin/Etoposide And Concurrent Thoracic Radiotherapy For Limited Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: etoposide
* Drug: tirapazamine
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed limited stage small cell lung cancer (SCLC) No malignant pericardial or pleural effusions, including any of the following: Cytologically positive effusions Exudative effusions not attributable to other etiologies No brain metastases Disease (measurable or non-measurable) must be present outside the area of prior surgical resection PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 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 OR Creatinine clearance at least 60 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception No symptomatic sensory neuropathy grade 1 or greater No other malignancy within past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other stage I or II cancer in complete remission No other medical illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for SCLC Chemotherapy: No prior systemic chemotherapy for SCLC Endocrine therapy: Not specified Radiotherapy: No prior thoracic radiotherapy for SCLC 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemo/RT with tirapazamine<br>induction and consolidation: cisplatin, etoposide, tirapazamine, radiation therapy | Drug: cisplatin<br>* During induction: 50 mg/m2/day, IV on Days 1, 8, 29, 36. 1 hour infusion During consolidation: 60 mg/m2, IV on Day 1 only at approximately Week 11, Week 14. 1 hour infusion.<br>* Other names: platinol;Drug: etoposide<br>* During induction: 50 mg/m2/day, IV on Days 1 - 5, 29 - 33. 1 hour infusion During consolidation: 120 mg/m2, IV on Days 1, 2 and 3 at approximately Week 11, Week 14. 1 hour infusion.<br>* Other names: VP-16;Drug: tirapazamine<br>* During induction: Phase I low dose: 260 mg/m2/day, IV on Days 1, 8, 29, 36. 1 hour infusion Phase II high dose: 330 mg/m2/day, IV on Days 1, 8, 29, 36 1 hour infusion During consolidation: 330 mg/ m2, IV Day 1 only at approximately Week 11, Week 14. 1 hour infusion.<br>Radiation: radiation therapy<br>* Radiotherapy should begin within 1 - 3 hours after completion of TPZ infusion on Day 1 of Cycle 1 of induction chemotherapy as outlined above. Computed tomography based treatment planning is strongly recommended.The primary tumor, adjacent mediastinum and other targeted lymph nodes shall receive 4,500 cGy in 25 fractions, five days/week at 180 cGy daily. A 1,600 cGy boost to areas of gross disease will be delivered through reduced off-spinal cord fields in eight fractions, five days/week at 200 cGy daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and Toxicity | If ten or more patients experience either Grade 3 or greater esophagitis or pneumonitis at any dose level, the trial will be stopped. Nine or fewer patients experiencing either of these toxicities will be evidence that the dose can be escalated to the next level. | toxicity is assessed weekly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limited stage small cell lung cancer