Combination Chemotherapy in Treating Patients With Extensive-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. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating extensive-stage small cell lung cancer. PURPOSE: Randomized phase III trial to compare different chemotherapy regimens in treating patients who have extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with chemotherapy-naive extensive stage small cell lung cancer treated with cisplatin and oral topotecan vs cisplatin and etoposide. Compare the response rates, response duration, and time to progression in patients treated with these regimens. Compare the tolerability of these regimens in these patients. Compare the patient-perceived disease status and well being in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender, ECOG performance status (0 vs 1 vs 2), lactate dehydrogenase (less than 1.5 times upper limit of normal (ULN) vs 1.5 times ULN or greater), and country. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral topotecan once daily on days 1-5 and cisplatin IV on day 5. Arm II: Patients receive cisplatin IV on day 1 and etoposide IV over at least 30 minutes on days 1-3. Treatment in both arms repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, prior to each course, at 4 weeks after study, and then every 4 weeks for 16 weeks. Patients are followed at 4 weeks, every 4 weeks for 16 weeks, and then every 3 months thereafter. PROJECTED ACCRUAL: Approximately 760 patients (380 per treatment arm) will be accrued for this study within 18 months.

Official Title
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An Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment For Chemotherapy-Naive Patients With Extensive Disease - Small Cell Lung

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: etoposide
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed extensive stage small cell lung carcinoma (SCLC) No prior chemotherapy for SCLC OR No chemotherapy within 5 years of diagnosis of SCLC Prior radiotherapy to measurable or nonmeasurable disease field allowed provided radiotherapy was completed at least 6 weeks ago and the disease is demonstrated to be progressing No clinical signs or symptoms of brain and/or leptomeningeal metastases by CT scan or MRI Brain and/or leptomeningeal metastases that are asymptomatic on neurologic exam are allowed provided metastases do not require corticosteroid therapy to control symptoms PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Hemoglobin at least 9.0 g/dL WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Neutrophil count at least 1,500/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT and SGPT no greater than 2 times the upper limit of normal (ULN) (5 times ULN if liver metastases present) Alkaline phosphatase no greater than 2 times ULN (5 times ULN if liver metastases present) Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No pre-existing renal impairment that would preclude cisplatin use Gastrointestinal: No clinical evidence of any gastrointestinal (GI) conditions including: Removal of a portion of the stomach History of recent obstruction of the GI tract GI autonomic neuropathy Ulcerative colitis Crohn's disease Malabsorption syndrome Treatment with cyclosporine that would alter absorption or GI motility No other conditions that would preclude absorption of oral topotecan Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 3 months prior to study, during, and for at least 1 month after study No active infection No other prior or concurrent malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or localized low-grade prostate cancer No other concurrent severe medical problems that would expose the patient to extreme risk or preclude study compliance No prior allergic reactions to compounds chemically related to study drugs No pre-existing hearing impairment that would preclude cisplatin use No overall medical condition for which study drugs would be inappropriate PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy for SCLC Chemotherapy: See Disease Characteristics No other concurrent chemotherapy for SCLC Endocrine therapy: See Disease Characteristics No concurrent hormonal therapy for SCLC Radiotherapy: See Disease Characteristics At least 24 hours since prior radiotherapy with no expected bone marrow suppression Recovered from prior palliative radiotherapy (e.g, nausea and vomiting from radiation of the epigastrium) No concurrent radiotherapy for SCLC No concurrent radiotherapy for palliation of bone metastases or CNS lesions unless approved by the investigator Surgery: At least 3 weeks since prior major surgery (a shorter period is allowed if deemed in the best interest of the patient) Other: More than 30 days or 5 half-lives (whichever is longer) since prior investigational drugs No other concurrent investigational therapy for SCLC No concurrent cyclosporine No concurrent drugs that would preclude absorption of oral topotecan

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: oral topotecan plus cisplatin IV<br>oral topotecan once daily on days 1-5 and cisplatin IV on day 5 | Drug: cisplatin<br> <br> Drug: topotecan hydrochloride<br> <br> |
| Experimental: Cisplatin IV plus etoposide IV<br>Cisplatin IV on day 1 and etoposide IV over at least 30 minutes | Drug: cisplatin<br> <br> Drug: etoposide<br> <br> |

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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extensive stage small cell lung cancer, recurrent small cell lung cancer