Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. An autologous peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ifosfamide when given together with paclitaxel and carboplatin followed by an autologous stem cell transplant and to see how well they work in treating patients with germ cell tumors that did not respond to cisplatin.
Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Testicular Germ Cell Tumor
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Response [ Time Frame: 2 year ] [ Designated as safety issue: No ]
Response assessed at the completion of therapy (after four to five cycles of chemotherapy and after surgery if necessary)
Complete Response (CR): A complete response is defined as one of the following:
- Complete disappearance of all clinical and radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy).
- Complete disappearance of all biochemical evidence of disease with resection of residual radiographic masses that prove to be negative for residual GCT; this includes both mature teratoma and necrotic debris (CR to chemotherapy) for a minimum of 4 weeks.
- Complete disappearance of all biochemical evidence of disease with complete surgical excision of all residual radiographic masses that, if pathologically positive for residual malignant GCT, show margins to microscopically free of disease (CR to chemotherapy + surgery). Patients must be free of disease for a minimum of 4 weeks.
- Maximum Tolerated Dose of Ifosfamide [ Time Frame: 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||February 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Experimental: chemotherapy with Stem Cell Support
This is a phase I/II trial of sequential accelerated chemotherapy cycles with paclitaxel/ifosfamide and paclitaxel/ifosfamide and carboplatin administered with G-CSF and PBSC support. During phase I, carboplatin, ifosfamide, and paclitaxel will be dose escalated to determine the MTD. Additional patients will be enrolled in the Phase II portion of the study following the determination of the MTD of Ifosfamide and paclitaxel, to bring the total possible number of patients treated at the MTD to 38.
|Biological: filgrastim Drug: carboplatin Drug: ifosfamide Drug: paclitaxel Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation|
- 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.
- 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 annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423852
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Darren Feldman, MD||Memorial Sloan Kettering Cancer Center|