Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy 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. PURPOSE: This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well they work in treating patients with stage II or stage III non-seminomatous germ cell tumors.

Detailed Description
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OBJECTIVES: Compare progression-free survival rates of patients with poor prognosis stage II or III non-seminomatous germ cell tumors with an unfavorable decrease of tumor markers after treatment with 1 course of bleomycin, etoposide, and cisplatin followed by subsequent treatment with 3 additional courses of bleomycin, etoposide, and cisplatin OR dose-dense sequential combination chemotherapy. Compare overall survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients with a favorable decrease of tumor markers after 1 course of BEP receive 3 additional courses of BEP. Patients with an unfavorable decrease of tumor markers after 1 course of BEP are randomized to 1 of 2 treatment arms. Arm I: Patients receive 3 additional courses of BEP. Arm II: Patients receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide. PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study.

Official Title
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A Risk-Adapted Strategy of the Use of Dose-Dense Chemotherapy in Patients With Poor-Prognosis Disseminated Non-Seminomatous Germ Cell Tumors

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

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of non-seminomatous germ cell tumors (NSGCT) as evidenced by 1 of the following criteria: Histologically confirmed NSGCT Clinical evidence of disease AND high serum human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) levels Clinical stage II-III disease (disseminated disease) Testicular, retroperitoneal, or mediastinal primary site Poor prognosis disease, meeting 1 of the following criteria: Mediastinal primary site Non-pulmonary visceral metastases One of the following lab values: HCG > 50,000 UI/L AFP > 10,000 ng/mL Lactate dehydrogenase > 10 times upper limit of normal (ULN) PATIENT CHARACTERISTICS: Age Over 16 Performance status Not specified Life expectancy Not specified Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times ULN Renal Creatinine clearance > 60 mL/min Other No other prior malignancy except basal cell skin cancer No HIV positivity 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: 120 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
Interventional Model Description: Phase 3 trial with direct individual benefit, randomized, open-label, multicenter, parallel groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP). | Biological: bleomycin sulfate<br>* At least one course administered<br>Drug: cisplatin<br>* At least one course administered<br>Drug: etoposide<br>* At least one course administered<br>|
| Experimental: Arm II<br>Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide. | Biological: bleomycin sulfate<br>* At least one course administered<br>Drug: cisplatin<br>* At least one course administered<br>Drug: etoposide<br>* At least one course administered<br>Drug: ifosfamide<br>* Given in a dose-dense sequential fashion<br>Drug: oxaliplatin<br>* Given in a dose-dense sequential fashion<br>Drug: paclitaxel<br>* Given in a dose-dense sequential fashion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Rate After 1 Course of Treatment | Primary objective is to compare the progression-free survival of participants after 1 cycle of treatment, treated randomly by 3 additional cycles of BEP (Arm I) or by T-BEP-Oxaliplatin/cisplatin-ifosfamide-Bleomycin (Arm II). The median progression-free survival rate was defined as the median percentage of participants alive without disease progression after 1 course of treatment. | 3 years from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | To evaluated the overall survival in both groups in participants presenting fast and slow decrease in serum levels of tumor markers. The median overall survival was defined as the median percentage of participants alive after 1 course of treatment. | 3 years from randomization | 

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