Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin

Phase 1

Completed

• Conditions: Ovarian Cancer; Testicular Germ Cell Tumor; Brain and Central Nervous System Tumors; Teratoma; Extragonadal Germ Cell Tumor
• Interventions: Biological: filgrastim; Drug: carboplatin; Drug: ifosfamide; Drug: paclitaxel; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

• Registration Number: NCT00423852
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

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.

Detailed Description

OBJECTIVES:

* 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 annually thereafter.

Study Timeline

• Study Start: 2006-08
• Study First Submitted: 2007-01-16
• Study First Submitted QC: 2007-01-16
• Study First Posted: 2007-01-18
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Results First Submitted: 2015-12-17
• Status Verified: 2016-04
• Results First Submitted QC: 2016-04-12
• Last Update Submitted: 2016-04-12
• Results First Posted: 2016-05-18
• Last Update Posted: 2016-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
chemotherapy with Stem Cell Support	autologous hematopoietic stem cell transplantation	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.
chemotherapy with Stem Cell Support	filgrastim	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.
chemotherapy with Stem Cell Support	peripheral blood stem cell transplantation	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.
chemotherapy with Stem Cell Support	paclitaxel	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.
chemotherapy with Stem Cell Support	carboplatin	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.
chemotherapy with Stem Cell Support	ifosfamide	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.

Primary Outcome Measures

Name	Time	Method
Response	2 year	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	4 years

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States