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 or peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating men with germ cell tumors.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bone marrow or peripheral stem cell transplantation in treating men with previously untreated germ cell tumors.

Condition	Treatment or Intervention	Phase
childhood extragonadal malignant germ cell tumor childhood malignant testicular germ cell tumor childhood mature and immature teratomas extragonadal germ cell tumor Testicular Cancer	Drug: bleomycin  Drug: carboplatin  Drug: cisplatin  Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Procedure: autologous bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of bleomycin, etoposide, and cisplatin (BEP) with or without high-dose carboplatin, etoposide, and cyclophosphamide plus autologous bone marrow or peripheral blood stem cell transplantation in male patients with poor- or intermediate-risk germ cell tumors.
• Compare the toxicity of these regimens in these patients.
• Compare prospectively the prognosis in terms of the rate of decline of the serum tumor markers, human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), in patients treated with these regimens.
• Correlate hCG and AFP with complete response and survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and risk status (poor vs intermediate). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bleomycin IV on days 1, 8, and 15 and etoposide (VP-16) IV over 30-60 minutes and cisplatin (CDDP) IV over 30-60 minutes on days 1-5 (BEP). Filgrastim (G-CSF) is administered subcutaneously (SC) on days 7-16 or until blood counts recover. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. G-CSF is discontinued 24 hours before initiating subsequent courses of chemotherapy, and withheld on days of bleomycin administration.
• Arm II: Patients receive 2 courses of BEP and G-CSF as in arm I. Patients who have no marrow involvement with tumor undergo harvest of autologous bone marrow before the first or second course of BEP. Patients who have bone marrow involvement with tumor undergo harvest of G-CSF-mobilized autologous peripheral blood stem cells (PBSC) on days 17-21 of the first and/or second courses of BEP. When blood counts recover, patients receive high-dose intensification comprising carboplatin IV over 1 hour, VP-16 IV over 30-60 minutes, and cyclophosphamide IV over 1 hour on days -5 to -3. Autologous bone marrow or PBSC are reinfused over 15-20 minutes on day 0. G-CSF is administered SC beginning 24 hours after transplantation and continuing until blood counts recover. Beginning 1-3 weeks after hospital discharge for the first transplantation and after recovery from any toxic effects, patients with a Karnofsky performance status of 70-100% receive a second course of high-dose intensification plus a second bone marrow or PBSC transplantation in the absence of disease progression or unacceptable toxicity. Patients on both arms with brain metastases at presentation undergo radiotherapy and/or surgery concurrently with BEP, if medically indicated.

Patients with normal alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG) tumor marker levels after completion of treatment on arm I or II undergo surgical resection of all residual masses. Patients who have no residual malignant tumor or undergo complete resection of only a mature teratoma receive no further therapy. Patients on arm I who undergo complete resection of residual malignant tumor receive 2 additional courses of VP-16 and CDDP without bleomycin. Patients on arm II who undergo complete resection of residual malignant tumor receive no additional chemotherapy. Patients with an unresectable residual malignant tumor receive additional therapy at the discretion of the treating physician. Patients with residual tumor marker (AFP and hCG) positivity after treatment on arm I or II undergo resection of residual masses if tumor marker values fall to normal by marker half-life.

PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 4.4 years.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven poor-risk, nonseminoma germ cell tumor
• Must meet 1 of the following 3 conditions:
• Testis or retroperitoneal primary site without visceral metastasis but with any of the following tumor marker values:
• Lactic dehydrogenase (LDH) greater than 10 times upper limit of normal (ULN)
• Human chorionic gonadotropin (hCG) greater than 50,000 IU/L
• Alpha-fetoprotein (AFP) greater than 10,000 ng/mL
• Testis or retroperitoneal primary site with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values), including the following:
• Bone
• Brain
• Liver
• Other nonpulmonary viscera (e.g., skin, spleen)
• Mediastinal primary site, regardless of presence/absence of visceral metastasis or tumor marker values OR
• Histologically proven intermediate-risk, nonseminoma germ cell tumor
• Testis or retroperitoneal primary site with no visceral metastasis (except lung), and with any of the following tumor marker values:
• LDH 3-10 times ULN
• hCG 5,000-50,000 IU/L
• AFP 1,000-10,000 ng/mL OR
• Histologically proven intermediate-risk, seminoma germ cell tumor with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values or primary site), including the following:
• Bone
• Brain
• Liver
• Other nonpulmonary visceral metastasis (e.g., skin, spleen)
• Histologic confirmation may be delayed, at the discretion of the protocol chairman, until after initiation of study therapy for patients with a testicular mass and elevated AFP or hCG if medical circumstances warrant immediate treatment
• Measurable or evaluable disease
• Concurrent registration on protocol MSKCC-89076 (SWOG-9345) for tumor biology studies required

PATIENT CHARACTERISTICS: Age:

• 12 and over

Sex:

• Male

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• See Disease Characteristics

Renal:

• Creatinine no greater than ULN* OR
• Creatinine clearance greater than 50 mL/min* NOTE: * Abnormal levels due to ureteral obstruction by tumor allowed at the discretion of the protocol chairman

Other:

• HIV negative
• No other concurrent malignancy except nonmelanomatous skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 30 days since prior radiotherapy except for brain metastases or documented disease progression
• Recovered from the toxic effects of any prior radiotherapy

Surgery:

• Recovered from the effects of any recent surgery

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010,  United States
      John Muir Medical Center, Walnut Creek,  California,  94598,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      St. Joseph Hospital - Orange, Orange,  California,  92868,  United States
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
      Sutter Cancer Center, Sacramento,  California,  95816,  United States
      Sutter Health Western Division Cancer Research Group, Greenbrae,  California,  94904,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center, West Palm Beach,  Florida,  33401,  United States
      Memorial Regional Hospital Comprehensive Cancer Center, Hollywood,  Florida,  33021,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813-2424,  United States
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Idaho
      Mountain States Tumor Institute, Boise,  Idaho,  83712,  United States
Illinois
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      Saint Anthony Medical Center, Rockford,  Illinois,  61108,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
      Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States
      Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States
      Mercy Medical Center, Des Moines,  Iowa,  50314,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7390,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Tuft-New England Medical Center, Boston,  Massachusetts,  02111,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Lakeland Medical Center - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0330,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      Alegent Health-Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Cooper University Hospital, Camden,  New Jersey,  08103,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Morristown Memorial Hospital, Morristown,  New Jersey,  07962,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States
      James P. Wilmot Cancer Center, Rochester,  New York,  14642,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
      Weill Medical College of Cornell University, New York,  New York,  10021,  United States
North Carolina
      Cape Fear Valley Health System, Fayetteville,  North Carolina,  28302-2000,  United States
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lenoir Memorial Hospital Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
      NorthEast Oncology Associates, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
North Dakota
      Veterans Affairs Medical Center - Fargo, Fargo,  North Dakota,  58102,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      Oregon Cancer Institute, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15236,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Danville Radiation Therapy Center, Memphis,  Tennessee,  38104,  United States
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38103,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
      Texas Tech University Health Science Center, Lubbock,  Texas,  79415,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Vermont
      Fletcher Allen Health Care - University Health Center Campus, Burlington,  Vermont,  05401,  United States
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22901,  United States
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Oncology and Hematology Associates of Southwest Virginia, Inc., Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      Ministry Medical Group - Northern Region, Rhinelander,  Wisconsin,  54501,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru
Puerto Rico
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico
      University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico

Study chairs or principal investigators

Robert J. Motzer, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   
Patrick J. Loehrer, MD,  Study Chair,  Indiana University Cancer Center   
Kim Allyson Margolin, MD,  Study Chair,  Beckman Research Institute   
Eric J. Small, MD,  Study Chair,  University of California, San Francisco   

Study ID Numbers:  CDR0000063820; MSKCC-94076; CLB-99812; E-3894; SWOG-9442; NCI-T94-0086D
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002596
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08