Phase I/II Trial of Sequential Paclitaxel/Ifosfamide Followed by Dose-Escalated, Dose-Intensive Carboplatin, Paclitaxel and Ifosfamide With Stem Cell Support in Cisplatin-Resistant Germ Cell Tumor Patients
- Determine the safety of paclitaxel and ifosfamide followed by dose-escalated,
dose-intensive paclitaxel, carboplatin, and ifosfamide with autologous peripheral blood
stem cell support in patients with cisplatin-resistant germ cell tumor. (Phase I)
- Determine the maximum tolerated dose of paclitaxel, carboplatin, and ifosfamide when
given with a high-dose treatment program in these patients. (Phase I)
- Determine the efficacy of this regimen when given as salvage therapy in the second-line
or third-line setting, in terms of complete response, in these patients. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of paclitaxel, carboplatin, and ifosfamide
followed by a phase II, open-label study.
- Phase I:
- Paclitaxel, ifosfamide, and autologous peripheral blood stem cell (PBSC)
collection: Patients receive paclitaxel IV over 3 hours on day 1 and ifosfamide IV
over 2 hours on days 1-3. Patients undergo leukapheresis on days 11-13. Patients
also receive filgrastim (G-CSF) subcutaneously (SC) twice daily beginning on day 3
and continuing until leukapheresis is completed. Beginning on day 14 or 21,
patients may receive a second course of paclitaxel, ifosfamide, and G-CSF.
Patients may also undergo additional leukapheresis.
- Paclitaxel, carboplatin, ifosfamide, and autologous PBSC transplantation: Patients
receive paclitaxel IV over 3 hours, high-dose carboplatin IV over 30 minutes, and
ifosfamide IV over 4 hours on days 1-3. Patients also receive G-CSF SC beginning
on day 3 and continuing until blood counts recover. Patients undergo reinfusion of
autologous PBSCs on day 5. Treatment repeats every 21-28 days for 3 courses in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of paclitaxel, carboplatin, and ifosfamide
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive treatment as in phase I with paclitaxel, carboplatin, and
ifosfamide at the MTD determined in phase I.
After completion of study treatment, patients are followed periodically for 1 year and then
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response (complete and partial)
Darren Feldman, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|