RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known whether chemotherapy plus peripheral stem cell transplantation is more effective than chemotherapy alone.

PURPOSE: This randomized phase III trial is studying combination chemotherapy to see how well it works when given with peripheral stem cell transplantation and comparing it to combination chemotherapy alone in treating men with previously untreated germ cell cancer.

Condition	Treatment or Intervention	Phase
bone metastases brain metastases liver metastases Mediastinal Cancer Testicular Cancer	Drug: bleomycin  Drug: cisplatin  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: peripheral blood stem cell transplantation	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of standard cisplatin, etoposide, and ifosfamide (VIP) followed by sequential high-dose VIP and stem cell rescue versus bleomycin, etoposide, and cisplatin (BEP) in men with previously untreated poor-prognosis germ cell cancer.
• Compare the acute and late toxicities of these treatment regimens in this patient population.
• Compare these regimens in terms of failure-free survival, response rate, and overall survival in these patients.
• Evaluate the quality of life in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, primary mediastinal germ cell tumor (yes vs no), and nonpulmonary visceral metastases (liver vs bone vs brain). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive etoposide IV over 1 hour followed by cisplatin IV over 1 hour on days 1-5 and bleomycin IV over 30 minutes on days 2, 8, and 15. Treatment repeats every 3 weeks for 4 courses.
• Patients receive 1 course of standard dose chemotherapy consisting of etoposide IV over 1 hour followed by cisplatin IV over 1 hour and ifosfamide IV over 1 hour on days 1-5. Peripheral blood stem cells (PBSC) are harvested around day 12-15. Patients also receive daily filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until PBSC collection is complete. After day 21, patients receive high-dose chemotherapy consisting of etoposide IV over 1 hour followed by cisplatin IV over 1 hour, and ifosfamide IV over 1 hour on days -6 through -2. PBSCs are infused on day 0. Patients receive daily G-CSF subcutaneously beginning on day 1 and continuing through day 19 or until blood counts have recovered. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before chemotherapy, at 6 months, and at 2 years after treatment.

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 annually thereafter.

PROJECTED ACCRUAL: A total of 222 patients (111 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  16 Years   -   50 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven germ cell cancer
• Nonseminoma OR
• Combined seminoma and nonseminoma
• Poor prognosis (nonseminoma):
• Testis/retroperitoneal primary AND
• One of the following poor tumor markers
• AFP greater than 10,000 iu/L
• HCG greater than 50,000 iu/L
• LDH greater than 10 times upper limit of normal OR
• Nonpulmonary visceral metastases (i.e., liver, bone, or brain) OR
• Mediastinal primary

PATIENT CHARACTERISTICS: Age:

• 16 to 50

Sex:

• Male

Performance status:

• WHO 0-3

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 upper limit of normal (ULN)
• AST no greater than 2 times ULN

Renal:

• Creatinine clearance at least 60 mL/min (unless due to obstructive uropathy correctable by nephrostomy)

Other:

• No other malignancy except basal cell skin cancer
• No neuropathy
• No other serious illness or medical condition
• No psychological, familial, sociological, or geographical condition that would prevent compliance

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Concurrent radiotherapy for brain metastases allowed

Surgery:

• Concurrent surgery for brain metastases allowed

Austria
      Kaiser Franz Josef Hospital, Vienna (Wien),  A-1100,  Austria; Recruiting
Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
Denmark
      Aarhus University Hospital - Aarhus Sygehus - Norrebrogade, Aarhus,  DK-8000,  Denmark; Recruiting
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
Germany
      Johannes Gutenberg University, Mainz,  D-55101,  Germany; Recruiting
      Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet, Greifswald,  D-17487,  Germany; Recruiting
      Klinikum der Universitaet Regensburg, Regensburg,  D-93053,  Germany; Recruiting
      Klinikum Nuernberg - Klinikum Nord, Nuernberg,  D-90419,  Germany; Recruiting
      Klinikum Rechts Der Isar - Technische Universitaet Muenchen, Munich (Muenchen),  D-81675,  Germany; Recruiting
      Knappschaft Krankenhaus, Bochum-Langendreer,  D-44892,  Germany; Recruiting
      Martin Luther Universitaet, Halle (Saale),  DOH-06112,  Germany; Recruiting
      St. Johannes Hospital - Medical Klinik II, Duisburg,  D-47166,  Germany; Recruiting
      Staedtische Kliniken Frankfurt am Main - Hoechst, Frankfurt,  D-65929,  Germany; Recruiting
      Staedtisches Klinikum Dessau, Dessau,  D-06822,  Germany; Recruiting
      Universitaetsklinikum Bonn, Bonn,  D-53105,  Germany; Recruiting
      Universitaetsklinikum Essen, ESSEN,  D-45122,  Germany; Recruiting
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany; Recruiting
      Universitatsklinik - Saarland, Homburg,  D-66421,  Germany; Recruiting
Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy; Recruiting
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
      University Medical Center Rotterdam at Erasmus Medical Center, Rotterdam,  3000 CA,  Netherlands; Recruiting
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway; Recruiting
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02 781,  Poland; Recruiting
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia; Recruiting
Spain
      Hospital Clinico Universitario Lozano Blesa, Zaragoza,  50009,  Spain; Recruiting
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain; Recruiting
      Hospital Donostia, San Sebastian,  20080,  Spain; Recruiting
      Hospital Universitario "Virgen de la Victoria" Malaga, Malaga,  29010,  Spain; Recruiting
      Hospital Universitario LA FE, Valencia,  46009,  Spain; Recruiting
      Institut Catala D'Oncologia, Barcelona,  08907,  Spain; Recruiting
Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland; Recruiting
United Kingdom, England
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom; Recruiting

Study chairs or principal investigators

Gedske Daugaard, MD, DMSc,  Rigshospitalet   

Study ID Numbers:  CDR0000067134; EORTC-30974; NCT00003941
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003941
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08