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Phase III Randomized Study 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 Previously Untreated Poor- or Intermediate-Risk Germ Cell Tumors
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase III | Treatment | Completed | 12 and over | MSKCC-94076 CLB-99812, E-3894, SWOG-9442, NCI-T94-0086D, NCT00002596, T94-0086 |
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.
Entry 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
Prior/Concurrent Therapy:
Biologic therapy: Chemotherapy: - No prior chemotherapy
- No other concurrent chemotherapy
Endocrine therapy: 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
Patient Characteristics:
Age: Sex: Performance status: Life expectancy: 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
Expected Enrollment 270A total of 270 patients (135 per treatment arm) will be accrued for this study
within 4.4 years. 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. Published ResultsMotzer RJ, Nichols CJ, Margolin KA, et al.: Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25 (3): 247-56, 2007.[PUBMED Abstract] Bajorin DF, Nichols CR, Margolin KA, et al.: Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): a cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB. [Abstract] J Clin Oncol 24 (Suppl 18): A-4510, 2006.
Trial Contact Information
Trial Lead Organizations Memorial Sloan-Kettering Cancer Center | | | Robert Motzer, MD, Protocol chair | | Ph: 646-422-4312; 800-525-2225 |
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Eastern Cooperative Oncology Group | | | Patrick Loehrer, MD, Protocol chair | | Ph: 317-278-7418; 888-600-4822 |
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Southwest Oncology Group | | | Kim Margolin, MD, Protocol chair(Contact information may not be current) | | | |
Cancer and Leukemia Group B | | | Eric Small, MD, Protocol chair | | Ph: 415-353-7095; 800-888-8664 |
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Registry Information | | Official Title | | RANDOMIZED MULTIINSTITUTIONAL PHASE III TRIAL OF BEP AND HIGH DOSE CHEMOTHERAPY VERSUS BEP ALONE IN PREVIOUSLY UNTREATED PATIENTS WITH POOR RISK GERM CELL TUMORS | | Trial Start Date | | 1994-09-08 | | Registered in ClinicalTrials.gov | | NCT00002596 | | Date Submitted to PDQ | | 1994-09-08 | | Information Last Verified | | 2003-10-15 | | NCI Grant/Contract Number | | CA05826, CA08748 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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