Trial Information

A Randomized Phase III Study of Sequential High-Dose Cisplatinum/Etoposide/Ifosfamide Plus Stem Cell Support Versus BEP in Patients With Poor Prognosis Germ Cell Cancer

OBJECTIVES:

- Compare the efficacy of standard cisplatin, etoposide, and ifosfamide (VIP) followed by
sequential high-dose VIP and stem cell rescue versus bleomycin, etoposide, and
cisplatin (BEP) in men with previously untreated poor-prognosis germ cell cancer.

- Compare the acute and late toxicities of these treatment regimens in this patient
population.

- Compare these regimens in terms of failure-free survival, response rate, and overall
survival in these patients.

- Evaluate the quality of life in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
center, primary mediastinal germ cell tumor (yes vs no), and nonpulmonary visceral
metastases (liver vs bone vs brain). Patients are randomized to one of two treatment arms.

- Arm I: Patients receive etoposide IV over 1 hour followed by cisplatin IV over 1 hour
on days 1-5 and bleomycin IV over 30 minutes on days 2, 8, and 15. Treatment repeats
every 3 weeks for 4 courses.

- Arm II: Patients receive 1 course of standard dose chemotherapy consisting of etoposide
IV over 1 hour followed by cisplatin IV over 1 hour and ifosfamide IV over 1 hour on
days 1-5. Peripheral blood stem cells (PBSC) are harvested around day 12-15. Patients
also receive daily filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing
until PBSC collection is complete.

After day 21, patients receive high-dose chemotherapy consisting of etoposide IV over 1 hour
followed by cisplatin IV over 1 hour, and ifosfamide IV over 1 hour on days -6 through -2.
PBSCs are infused on day 0. Patients receive daily G-CSF subcutaneously beginning on day 1
and continuing through day 19 or until blood counts have recovered. Treatment repeats every
3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before chemotherapy, at 6 months, and at 2 years after
treatment.

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

PROJECTED ACCRUAL: A total of 222 patients (111 per treatment arm) will be accrued for this
study within 2 years.