Combination Chemotherapy and 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 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. Combining chemotherapy with radiation therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy before, during, and after radiation therapy in treating patients who have limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of thoracic radiotherapy administered with cisplatin, etoposide, and amifostine preceded and followed by topotecan and paclitaxel in patients with limited stage small cell lung cancer (phase I closed to accrual as of 5/27/2004). Determine the two-year survival of this patient population treated with this regimen. Determine the two-year, progression-free local control rate in this patient population treated with this regimen. Assess the tolerability of this treatment regimen in these patients. Determine the antitumor activity of this regimen in these patients. Determine the overall survival and overall time to progression in this patient population treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of thoracic radiotherapy (TRT). Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses. After 2 courses of topotecan and paclitaxel, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT. At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation. Cohorts of 3-6 patients receive escalating doses of TRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity (phase I closed to accrual as of 5/27/2004). Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 3-73 patients will be accrued for this study (phase I closed to accrual as of 5/27/2004).

Official Title
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Phase I-II Study of Topotecan and Paclitaxel Followed by High-Dose Thoracic Radiation Therapy With Concomitant Cisplatin/Etoposide and Amifostine in Limited-Stage Small Cell Lung Cancer

Conditions
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Drug/Agent Toxicity by Tissue/Organ, Lung Cancer, Radiation Toxicity

Intervention / Treatment
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* Biological: filgrastim
* Drug: amifostine trihydrate
* Drug: cisplatin
* Drug: etoposide
* Drug: paclitaxel
* Drug: topotecan hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Limited disease confined to one hemithorax, the ipsilateral supraclavicular fossa, and encompassable within tolerable thoracic radiotherapy field Minimal pleural effusions (i.e., blunting of the costophrenic angle on chest x-ray or a small effusion on CT scan) allowed Measurable disease At least one lesion accurately measured in at least 1 dimension with longest diameter at least 20 mm PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 3 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease Pulmonary: FEV_1 at least 40% of predicted AND at least 1 liter Other: No uncontrolled infection No other severe underlying diseases No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas (carcinoma in situ) No grade 2 or greater peripheral neuropathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No hypersensitivity to E.coli-derived proteins, filgrastim (G-CSF), or any excipients of G-CSF PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No prior hemithorax radiotherapy Surgery Not specified Other No prior therapy for small cell lung cancer

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 |
| --- | --- |
| Experimental: topotecan + paclitaxel + filgrastim + TRT + radiation<br>Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses. After 2 courses of treatment, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT. At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation. Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years. | Biological: filgrastim<br> <br> Drug: amifostine trihydrate<br> <br> Drug: cisplatin<br> <br> Drug: etoposide<br> <br> Drug: paclitaxel<br> <br> Drug: topotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 2 years |  | at 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local progression-free survival at 2 years |  | at 2 years | 
| Overall survival |  | Up to 5 years | 
| Time to progression |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation toxicity, drug/agent toxicity by tissue/organ, limited stage small cell lung cancer