PHASE I/II TRIAL OF SEQUENTIAL TAXOL/IFOSFAMIDE AND DOSEINTENSIVE CARBOPLATIN/ETOPOSIDE WITH STEM CELL SUPPORT IN CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES
- Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide
with stem cell support in patients with unfavorable germ cell tumors with unfavorable
prognostic factors and resistance to cisplatin.
- Determine the efficacy of this regimen as salvage therapy in these patients.
- Escalate the dose of carboplatin based on a target area under the concentration time
curve and renal function, and determine the pharmacokinetics of carboplatin in selected
- Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic
progenitors in these patients.
OUTLINE: This is a dose escalation study of carboplatin.
- Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4
hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days
11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6
hours after completion of paclitaxel and ifosfamide infusions and continuing until the
last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the
absence of disease progression or unacceptable toxicity. Before beginning the first
course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case
insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable
to undergo harvest of ABM before the first course of chemotherapy undergo harvest of
ABM before beginning the second course of chemotherapy.
- Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV
over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5.
G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide
and carboplatin infusions and continuing until blood counts recover. G-CSF is held on
the morning of PBSC transplantation and restarted beginning 6 hours after completion of
PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of
disease progression or unacceptable toxicity. Patients with insufficient PBSC for the
second course receive PBSC combined with ABM. Patients with insufficient PBSC for the
third course receive ABM.
During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 3 of 6 patients experience dose-limiting toxicity.
After completion of parts A and B, some patients may undergo resection of residual masses.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Gnanamba V. Kondagunta, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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