Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin, vincristine, bleomycin, carboplatin, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating germ cell tumors. PURPOSE: This randomized phase II trial is studying two different combination chemotherapy regimens to compare how well they work in treating male patients with germ cell tumors.

Detailed Description
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OBJECTIVES: Primary Compare the response rate in patients with poor-prognosis extracranial nonseminoma germ cell tumors treated with intensive induction chemotherapy comprising cisplatin, vincristine, bleomycin, and carboplatin followed by bleomycin, etoposide phosphate, and cisplatin (BEP) vs standard BEP chemotherapy. Secondary Compare overall and progression-free survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to participating center, pre-protocol low-dose chemotherapy (yes vs no), and other clinically important factors. Patients are randomized to 1 of 2 treatment arms. Arm I (BEP): Patients receive bleomycin IV over 15 minutes once on day 1 or 2 and days 8 and 15 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (CBOP/BEP): Patients receive chemotherapy according to the following schedule: Weeks 1-6: Patients receive cisplatin IV over 6 hours on days 1, 2, 8, 15, 16, and 22 (OR over 4 hours on days 1-5 and 15-19); vincristine IV on days 1, 8, 15, 22, 29, and 36; bleomycin IV over 15 minutes on days 1, 15, 29, and 36 and bleomycin IV continuously on days 8-12 and 22-25; and carboplatin IV over 30-60 minutes on days 8 and 22. Weeks 7-15: Patients receive bleomycin IV continuously on days 1-5, 8-12, and 15-19 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for 4 courses. After completion of study treatment, patients are followed periodically for 5 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 88 patients will be accrued for this study.

Official Title
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Randomized Phase II Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP Chemotherapy in Poor Prognosis Male Germ Cell Tumors

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

Intervention / Treatment
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* Biological: bleomycin sulfate
* Drug: carboplatin
* Drug: cisplatin
* Drug: etoposide phosphate
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Nonseminoma germ cell tumor of any extracranial primary site diagnosed by 1 of the following methods: Histologic confirmation Alpha-fetoprotein (AFP) > 1,000 ng/mL or human chorionic gonadotropin (hCG) > 5,000 IU/L with appropriate clinical picture in a man < 45 years of age Poor prognosis features as defined by ≥ 1 of the following: AFP > 10,000 ng/mL hCG > 50,000 IU/L Lactic dehydrogenase > 10 times normal Nonpulmonary visceral metastases Mediastinal primary site PATIENT CHARACTERISTICS: Male WHO performance status 0-3 Glomerular filtration rate > 50 mL/min Less than 50 mL/min eligible if due to obstructive neuropathy that can be relieved by stenting or nephrostomy No comorbid condition that would prevent treatment Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior chemotherapy except low-dose chemotherapy to stabilize disease before study therapy

Ages Eligible for Study
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Minimum Age: 16 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bleomycin sulfate|nan|
|Drug: carboplatin|nan|
|Drug: cisplatin|nan|
|Drug: etoposide phosphate|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates to treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Progression-free survival |  |  | 
| Toxicity |  |  | 

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