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.

Condition	Treatment or Intervention	Phase
extragonadal germ cell tumor Testicular Cancer	Drug: bleomycin  Drug: cisplatin  Drug: etoposide  Drug: filgrastim  Drug: paclitaxel  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy	Phase II Phase III

Further Study Details: 

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.

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

Criteria

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

Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria; Recruiting
Belgium
      Institut Jules Bordet, Brussels,  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
France
      Centre Regional Francois Baclesse, Caen,  14076,  France; Recruiting
      Institut Claudius Regaud, Toulouse,  31052,  France; Recruiting
      Institut Gustave Roussy, Villejuif,  F-94805,  France; Recruiting
Germany
      Allgemeines Krankenhaus Hagen, Hagen,  D-58095,  Germany; Recruiting
      Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin, Berlin,  D-12200,  Germany; Recruiting
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany; Recruiting
      Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet, Greifswald,  D-17487,  Germany; Recruiting
      Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein,  D-67063,  Germany; Recruiting
      Klinikum der Stadt Mannheim, Mannheim,  D-68135,  Germany; Recruiting
      Klinikum der Universitaet Regensburg, Regensburg,  D-93053,  Germany; Recruiting
      Klinikum Kassel, Kassel,  D-34125,  Germany; Recruiting
      Klinikum Nuernberg - Klinikum Nord, Nuremberg,  D-90419,  Germany; Recruiting
      Klinikum Rechts Der Isar - Technische Universitaet Muenchen, Munich,  D-81675,  Germany; Recruiting
      Klinikum Schwerin, Schwerin,  D-19049,  Germany; Recruiting
      Martin Luther Universitaet, Halle,  DOH-06112,  Germany; Recruiting
      Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster, Muenster,  D-48149,  Germany; Recruiting
      Philipps-Universitaet Marburg Klinikum, Marburg,  D-35033,  Germany; Recruiting
      St. Johannes Hospital - Medical Klinik II, Duisburg,  D-47166,  Germany; Recruiting
      Universitaetsklinikum Bonn, Bonn,  D-53105,  Germany; Recruiting
      Universitaetsklinikum Essen, ESSEN,  D-45122,  Germany; Recruiting
      Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg, Magdeburg,  D-39120,  Germany; Recruiting
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany; Recruiting
      Universitatsklinik - Saarland, Homburg,  D-66421,  Germany; Recruiting
Hungary
      National Institute of Oncology, Budapest,  1125,  Hungary; Recruiting
Israel
      Assaf Harofeh Medical Center, Zerifin,  70300,  Israel; Recruiting
Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Jeroen Bosch Ziekenhuis, 's-Hertogenbosch,  5211 NL,  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
      University Medical Center Utrecht, Utrecht,  3584 CX,  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 General Universitari Vall d'Hebron, Barcelona,  08035,  Spain; Recruiting
      Hospital Sant Joan de Reus, Reus,  43201,  Spain; Recruiting
      Hospital Universidad Virgen Del Rocio, Sevilla,  E- 41013,  Spain; Recruiting
      Hospital Universitario "Virgen de la Victoria" Malaga, Malaga,  29010,  Spain; Recruiting
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain; Recruiting
      Hospital Universitario LA FE, Valencia,  46009,  Spain; Recruiting
      Hospital Universitario San Carlos, Madrid,  28040,  Spain; Recruiting
      Institut Catala d'Oncologia - Hospital Duran i Reynals, Barcelona,  08907,  Spain; Recruiting
United Kingdom, England
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
United Kingdom, Scotland
      Western Infirmary, Glasgow,  Scotland,  G11 6NT,  United Kingdom; Recruiting
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom; Recruiting

Study chairs or principal investigators

Ronald De Wit, MD, PhD,  Daniel Den Hoed Cancer Center at Erasmus Medical Center   

Study ID Numbers:  CDR0000066731; EORTC-30983; NCT00003643
Record last reviewed:  March 2005
Last Updated:  April 4, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003643
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08