Trial Information

RANDOMIZED MULTIINSTITUTIONAL PHASE III TRIAL OF BEP AND HIGH DOSE CHEMOTHERAPY VERSUS BEP ALONE IN PREVIOUSLY UNTREATED PATIENTS WITH POOR RISK GERM CELL TUMORS

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.