Combination Chemotherapy in Treating Men With Germ Cell 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 regimen of combination chemotherapy may be more effective for germ cell cancer. PURPOSE: This randomized phase II/III trial is studying two different regimens of combination chemotherapy and comparing how well they work in treating men with germ cell cancer.

Detailed Description
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OBJECTIVES: Phase II Compare the complete response rates in men with intermediate prognosis germ cell cancer treated with bleomycin, cisplatin, and etoposide (BEP) vs bleomycin, cisplatin, etoposide, and paclitaxel (T-BEP). Define the toxicity profile of T-BEP in these patients. Phase III Compare the disease-free survival of patients treated with these regimens. Compare the complete response rates and overall survival of patients treated with these regimens. Compare symptoms and aspects of quality of life at baseline and after treatment in patients treated with these regimens. Compare the acute and intermediate (1-2 years) side effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (seminoma vs non-seminoma) and hospital. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin IV and etoposide IV on days 1-5 and bleomycin IV on days 1, 8, and 15. Arm II: Patients receive cisplatin, etoposide, and bleomycin as in arm I and paclitaxel IV over 3 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-15. In both arms, treatment repeats every 3 weeks for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before treatment randomization and at 1 and 2 years after randomization. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 84-164 patients (42-82 per treatment arm) will be accrued for the phase II study. A total of 498 patients (249 per treatment arm) will be accrued for the phase III study. Accrual will be completed within 4 years.

Official Title
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Randomized Phase II/III Study of Taxol/Paclitaxel-BEP Versus BEP in Patients With Intermediate Prognosis Germ Cell Cancer

Conditions
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Teratoma, Extragonadal Germ Cell Tumor, Testicular Germ Cell Tumor

Intervention / Treatment
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* Biological: bleomycin sulfate
* Biological: filgrastim
* Drug: cisplatin
* Drug: etoposide
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven germ cell cancer Seminoma Non-seminoma Combined Intermediate prognosis Non-seminoma: Testis/retroperitoneal primary No non-pulmonary visceral metastases Meets 1 of the following criteria: Alpha-fetoprotein (AFP) 1,000- 10,000 IU/L Human chorionic gonadotropin (hCG) 5,000-50,000 IU/L Lactic dehydrogenase (LDH) 1.5 times-10 times upper limit of normal (ULN) Seminoma: Any primary site Any LDH and HCG AFP normal Non-pulmonary visceral metastases present PATIENT CHARACTERISTICS: Age: 16 to 50 Sex: Male Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.25 times ULN AST no greater than 2 times ULN Renal: Creatinine clearance at least 40 mL/min (unless due to obstructive uropathy which can be relieved by nephrostomy) Other: No pre-existing neuropathy No other malignancy except basal cell skin cancer No other serious illness or medical conditions incompatible with the protocol PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bleomycin sulfate|nan|
|Biological: filgrastim|nan|
|Drug: cisplatin|nan|
|Drug: etoposide|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival as measured by Logrank |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment as measured by normalized markers without residual viable cancer after CT scan or surgery |  |  | 
| Overall survival as measured by Logrank at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter |  |  | 
| Disease-free survival as measured by Logrank at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter |  |  | 
| Toxicity as measured by NCI-CTC v2.0 at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter |  |  | 
| Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, during treatment, and at years 1 and 2 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III malignant testicular germ cell tumor, testicular seminoma, testicular embryonal carcinoma, testicular choriocarcinoma, testicular yolk sac tumor, testicular embryonal carcinoma and teratoma, testicular embryonal carcinoma and teratoma with seminoma, testicular embryonal carcinoma and yolk sac tumor, testicular embryonal carcinoma and yolk sac tumor with seminoma, testicular embryonal carcinoma and seminoma, testicular yolk sac tumor and teratoma, testicular yolk sac tumor and teratoma with seminoma, testicular choriocarcinoma and yolk sac tumor, testicular choriocarcinoma and embryonal carcinoma, testicular choriocarcinoma and teratoma, testicular choriocarcinoma and seminoma, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, testicular immature teratoma, testicular mature teratoma, adult teratoma