Cisplatin, Etoposide, and Cyclophosphamide 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, such as cisplatin, etoposide, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cisplatin, etoposide, and cyclophosphamide together works in treating patients with extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety of cisplatin, etoposide, and cyclophosphamide in patients with extensive stage small cell lung cancer. Determine the effect of this regimen on circulating endothelial cells in the peripheral blood of these patients. Secondary Determine progression-free survival, tumor response rate, and overall survival in patients treated with this regimen. OUTLINE: This is a multicenter study. Induction therapy: Patients receive cisplatin IV over 30 minutes-2 hours on day 1, etoposide IV over 1-2 hours on days 1-3 OR etoposide IV on day 1 and orally twice daily on days 2-3, and oral cyclophosphamide twice daily on days 8-19. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance therapy: Patients receive oral cyclophosphamide twice daily in the absence of disease progression. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Official Title
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Pilot Study of a Combination of Standard Etoposide/Cisplatin and Metronomic Cyclophosphamide in Patients With Newly Diagnosed Extensive Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: cyclophosphamide
* Drug: etoposide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Extensive stage disease (i.e., disease beyond the hemithorax and cannot be encompassed safely by a tolerable radiation field) Measurable disease Concurrent CNS metastases allowed provided patient remains asymptomatic Radiotherapy or surgery for uncontrolled symptoms allowed before study entry PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8 g/dL (transfusion allowed) Hepatic ALT ≤ 2 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN Renal Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 60 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past year except adequately treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy Chemotherapy No prior chemotherapy Endocrine therapy Concurrent corticosteroids for brain metastases allowed Radiotherapy See Disease Characteristics Prior radiotherapy to any symptomatic site allowed provided the target site(s) was not previously irradiated No concurrent radiotherapy 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral cyclophosphamide plus standard cisplatin with etoposide<br>Etoposide 120 mg/m2 IV Days 1-3 or Etoposide 120 mg/ m2 IV Day1 followed by Etoposide 120 mg/ m2 PO BID Days 2-3 Cisplatin 60 mg/m2 IV Day 1 Every 21 days x 4 cycles Cyclophosphamide 25 mg PO BID Days 8-19 of each cycle | Drug: cisplatin<br>* 60 mg/m2 IV day 1, every 21 days for 4 cycles.<br>Drug: cyclophosphamide<br>* 25 mg by mouth BID days 8-19 or each cycle x 4 cycles. After restaging (if no progression) maintenance cyclophosphamide alone 25 mg by mouth BID daily until disease progression<br>* Other names: Cytoxan;Drug: etoposide<br>* 120 mg/m2 IV days 1-3 OR 120 mg/m2 IV day 1 and 120 mg/m2 by mouth BID days 2-3<br>* Other names: VP-16;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | From time of registration to 30 days post treatment of last cycle. | 
| Effect of metronomic chemotherapy on circulating endothelial cells | Collected cycle 1/day 1 of chemotherapy, Cycle 1/day 8, cycle 1/day 22, and then day 85 and 141, and at disease progression. | Baseline to progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Registration to time of progression | 
| Response rate |  | From Registration to time of disease progression | 
| Overall survival |  | From registration to time patient expires | 

 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