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: This randomized phase III trial is studying paclitaxel, ifosfamide, and cisplatin to
see how well they work compared to vinblastine, ifosfamide, and cisplatin in treating men
with progressive or recurrent metastatic germ cell tumors.
- 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.
- 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.
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
Northeast Alabama Regional Medical Center, Anniston, Alabama 36207, United States
Naval Medical Center - San Diego, San Diego, California 92134-3202, United States
Rebecca and John Moores UCSD Cancer Center, La Jolla, California 92093-0658, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, California 90048, United States
UCSF Comprehensive Cancer Center, San Francisco, California 94115, 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
CCOP - Christiana Care Health Services, Newark, Delaware 19713, United States
Lombardi Cancer Center at Georgetown University Medical 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 20307-5001, United States
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
Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States
Palm Beach Cancer Institute - West Palm Beach, West Palm Beach, Florida 33401, United States
CCOP - Evanston, Evanston, Illinois 60201, United States
CCOP - Illinois Oncology Research Association, Peoria, Illinois 61615-7828, United States
Louis A. Weiss Memorial Hospital, Chicago, Illinois 60640, United States
MBCCOP - University of Illinois at Chicago, Chicago, Illinois 60612, 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
West Suburban Center for Cancer Care, River Forest, Illinois 60305, United States
CCOP - Northern Indiana CR Consortium, South Bend, Indiana 46601, United States
Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne, Indiana 46885-5099, United States
Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242-1009, United States
Baptist Hospital East - Louisville, Louisville, Kentucky 40207, United States
Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore, Maryland 21201, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
UMASS Memorial Cancer Center - University Campus, Worcester, Massachusetts 01655, United States
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph, Michigan 49085, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Veterans Affairs Medical Center - Minneapolis, Minneapolis, Minnesota 55417, United States
CCOP - Kansas City, Kansas City, Missouri 64131, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States
Missouri Baptist Cancer Center, Saint Louis, Missouri 63131, United States
Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis, Missouri 63110, United States
Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia, Missouri 65201, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-7680, United States
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 Oncology-Hematology, PA - Hooksett, Hooksett, New Hampshire 03106, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States
Cancer Institute of New Jersey at the Cooper University Hospital, Camden, New Jersey 08103, United States
CCOP - North Shore University Hospital, Manhasset, New York 11030, United States
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse, New York 13057, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Mount Sinai Medical Center, New York, New York 10029, United States
New York Weill Cornell Cancer Center at Cornell University, New York, New York 10021, 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
SUNY Upstate Medical University Hospital, 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
Cape Fear Valley Medical Center, Fayetteville, North Carolina 28302-2000, United States
CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States
Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst, North Carolina 28374, 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
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
NorthEast Oncology Associates - Concord, Concord, North Carolina 28025, United States
Veterans Affairs Medical Center - Asheville, Asheville, North Carolina 28805-9913, United States
Veterans Affairs Medical Center - Durham, Durham, North Carolina 27705, United States
Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington, North Carolina 28402-9025, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus, Ohio 43210-1240, United States
Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh, Pennsylvania 15224, United States
McGill Cancer Centre at McGill University, Montreal, Quebec H2W 1S6, Canada
Miriam Hospital at Lifespan, Providence, Rhode Island 02906, United States
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390-8852, United States
Veterans Affairs Medical Center - Dallas, Dallas, Texas 75219, United States
Vermont Cancer Center at University of Vermont, Burlington, Vermont 05401-3498, United States
Martha Jefferson Hospital, Charlottesville, Virginia 22902, United States
MBCCOP - Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke, Virginia 24014, United States
Virginia Oncology Associates - Norfolk, Norfolk, Virginia 23502, United States
St. Mary's Medical Center, Huntington, West Virginia 25701, United States
Ministry Medical Group at Saint Mary's Hospital, Rhinelander, Wisconsin 54501, United States
