RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not known whether combining chemotherapy with bone marrow transplantation is a more effective treatment for men with germ cell tumors. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with bone marrow transplantation in treating men with relapsed germ cell tumors.

Condition	Treatment or Intervention	Phase
recurrent testicular cancer extragonadal germ cell tumor	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: surgery  Procedure: autologous bone marrow transplantation  Procedure: bone marrow transplantation  Procedure: peripheral blood stem cell transplantation  Drug: bone marrow ablation with stem cell support  Procedure: conventional surgery  Drug: carboplatin  Drug: cisplatin  Drug: cyclophosphamide  Drug: etoposide  Drug: ifosfamide  Drug: vinblastine	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the event-free survival of male patients with germ cell tumors in relapse or first partial remission treated with salvage therapy comprising cisplatin, etoposide, and ifosfamide (PEI) or vinblastine, ifosfamide, and cisplatin (VeIP) with or without high-dose carboplatin, etoposide, and cyclophosphamide, followed by autologous bone marrow and/or peripheral blood stem cell transplantation.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior complete remission to first-line treatment (yes vs no), primary site of disease (testicular vs retroperitoneal vs mediastinal), and lung metastases at study entry (yes vs no). Autologous bone marrow and peripheral blood stem cells (PBSC) are harvested. Part I (salvage): Patients are assigned to regimen A if they previously received vinblastine as part of a first-line treatment, such as cisplatin, vinblastine, and bleomycin (PVB) or cisplatin, cyclophosphamide, doxorubicin, vinblastine, and bleomycin (CISCA VB). Patients are assigned to regimen B if they previously received etoposide (VP-16) as part of a first-line treatment, such as bleomycin, VP-16, and cisplatin (BEP). Regimen A: Patients receive cisplatin IV over 2 hours, VP-16 IV over 2 hours, and ifosfamide IV over 1 hour on days 1-5 (PEI). Regimen B: Patients receive cisplatin and etoposide as in regimen A and vinblastine IV on days 1 and 2 (VeIP). Treatment on both regimens continues every 3 weeks for 2 courses. Patients with refractory disease at day 43 are taken off study. Part II: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive 2 additional courses of PEI or VeIP. Arm II: Patients receive 1 additional course of PEI or VeIP, followed by 1 course of high-dose carboplatin IV over 2 hours, VP-16 IV over 2 hours, and cyclophosphamide IV over 1 hour on days 1-4. Autologous bone marrow and/or PBSC are reinfused on day 7 of the fourth course for patients on both arms. Patients on both arms with residual disease after the fourth course may undergo surgery.

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of testicular or extragonadal male germ cell tumors; Must meet 1 of the following conditions after completion of platinum-based first-line chemotherapy: Complete remission (CR) followed by relapse; Partial remission (PR); Prior resection of viable malignancy with elevated tumor markers allowed
• Initial bulky disease with no CR (significantly reduced but still abnormal in plateau) allowed if there is an increase in biological tumor markers or development of new metastases
• Seminoma with relapse after CR or PR to cisplatin-based chemotherapy allowed
• No pure seminoma pre-treated with carboplatin
• No refractory disease (i.e., documented increase in tumor burden and/or serum tumor marker level during or within 1 month after platinum-containing chemotherapy)
• CNS involvement allowed

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: Prior radiotherapy for metastatic disease allowed
• Surgery: See Disease Characteristics; Prior surgery for metastatic disease allowed

--Patient Characteristics--

• Age: 16 and over
• Sex: Male
• Performance status: WHO 0-2 OR Karnofsky 50-100%
• Life expectancy: No limits on life expectancy due to severe non-malignant disease
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Cardiovascular: No severe cardiac disease that would interfere with study therapy
• Pulmonary: No severe pulmonary disease that would interfere with study therapy
• Other: HIV negative; No severe neurologic or metabolic disease that would interfere with study therapy; No psychological, socioeconomic, or geographic circumstances that would preclude study; No other concurrent malignancy

France
      Institut Gustave Roussy, Villejuif,  F-94805,  France

Study chairs or principal investigators

Jose-Louis Pico,  Study Chair,  Federation Nationale des Centres de Lutte Contre le Cancer   

Study ID Numbers:  CDR0000063579; FRE-IT94; NCI-F94-0019; FRE-FNCLCC-IT94
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002566
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08