RATIONALE: Drugs used in chemotherapy, such as ifosfamide, cisplatin, paclitaxel, and vinblastine, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether ifosfamide and cisplatin are more effective when combined with paclitaxel or vinblastine in treating germ cell tumors.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining ifosfamide and cisplatin with either paclitaxel or vinblastine in treating men who have progressive or recurrent metastatic germ cell tumors.

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

Further Study Details: 

OBJECTIVES: Primary

• Compare the overall survival of men with progressive or recurrent metastatic germ cell tumors treated with paclitaxel, ifosfamide, and cisplatin vs vinblastine, ifosfamide, and cisplatin as second-line therapy.

Secondary

• Compare the progression-free survival of patients treated with these regimens.
• Compare the toxicity profiles of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior complete response or partial response with negative markers for at least 6 months (yes vs no) and relapse at least 2 years after completing first-line chemotherapy for germ cell tumors (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 2-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-18 OR pegfilgrastim SC once within 24-72 hours after completion of chemotherapy.
• Arm II: Patients receive vinblastine IV on days 1 and 2 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 1-5. Patients also receive G-CSF SC on days 7-18 OR pegfilgrastim as in arm I. In both arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 470 patients (235 per treatment arm) will be accrued for this study within 5.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed germ cell tumor (GCT), including 1 of the following primary tumor sites:
• Seminoma
• Testis
• Retroperitoneum
• Mediastinum
• Other extragonadal site
• Nonseminoma
• Testis
• Retroperitoneum
• Other extragonadal site
• No tumor of the mediastinum
• Must have evidence of metastatic disease, including either of the following:
• Unidimensionally measurable lesions
• At least 20 mm by conventional techniques (e.g., physical exam for clinically palpable lymph nodes and superficial skin lesions or chest x-ray for clearly defined lung lesions surrounded by aerated lung) OR at least 10 mm by spiral CT scan or MRI
• Nonmeasurable lesions, including the following:
• Small lesions
• Bone lesions
• Pleural or pericardial effusions
• Ascites
• Irradiated lesions, unless progression is documented after radiotherapy
• Progressive or recurrent disease meeting at least 1 of the following criteria:
• Measurable progressive disease
• Biopsy-proven residual disease
• Persistently elevated or rising ß-human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) titers with no other clear cause for elevation
• Previously treated with 1 and only 1 regimen comprising etoposide and cisplatin with or without bleomycin AND exhibits clinical resistance by at least 1 of the following conditions after therapy*:
• Progressive GCT after a partial response to first-line therapy
• Relapse after complete response (CR) to first-line therapy, including partial response (PR) surgically converted to CR
• Second testicular primary with evidence of metastases after first-line therapy
• Relapse after adjuvant chemotherapy NOTE: *Patients failing to achieve PR or CR with first-line therapy as evidenced by rising markers or new disease within 4 weeks of first-line therapy are not eligible

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal* (ULN)
• AST and ALT ≤ 2.5 times ULN* NOTE: *Unless hepatic metastases are present

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Other

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior dose-intensive therapy with stem cell replacement

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior paclitaxel
• No prior docetaxel
• No prior ifosfamide
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• Concurrent or sequential radiotherapy to brain metastases allowed
• No other concurrent palliative radiotherapy

Surgery

• See Disease Characteristics
• Concurrent surgery for brain metastases allowed

Other

• Recovered from prior therapy

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Palm Beach Cancer Institute - West Palm Beach, West Palm Beach,  Florida,  33401,  United States; Recruiting
Illinois
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States; Recruiting
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Rhode Island
      Miriam Hospital at Lifespan, Providence,  Rhode Island,  02906,  United States; Recruiting
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States; Recruiting
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting
Wisconsin
      Ministry Medical Group at Saint Mary's Hospital, Rhinelander,  Wisconsin,  54501,  United States; Recruiting
Canada, Quebec
      McGill Cancer Centre at McGill University, Montreal,  Quebec,  H2W 1S6,  Canada; Recruiting

Study chairs or principal investigators

Robert J. Motzer, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000339340; CALGB-90106; NCT00072215
Record last reviewed:  July 2004
Last Updated:  April 5, 2005
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072215
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08