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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423852
• Other study ID #: 06-077
• Secondary ID: MSKCC-06077
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 16, 2007
• Last updated: February 6, 2013
• Start date: August 2006
• Est. completion date: February 2013

Study information

• Verified date: February 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed germ cell tumor (GCT)

• Primary CNS GCT allowed

• Unidimensionally measurable disease OR elevated serum tumor markers (alpha-fetoprotein and/or human chorionic gonadotropin)

• Advanced disease

• Disease resistant to a cisplatin-based chemotherapy regimen (i.e., failed to achieve a durable complete response to cisplatin)

• Known residual disease after post-chemotherapy surgery allowed

PATIENT CHARACTERISTICS:

• Platelet count = 100,000/mm^3

• WBC = 3,000/mm^3

• Creatinine clearance > 50 mL/min (unless due to tumor obstructing the ureters)

• AST and ALT < 2 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active infection

• Negative serology for HIV type I and II, human T-lymphotropic virus type I and II, hepatitis B or C virus, syphilis, and cytomegalovirus

• Hepatitis C negative serology by RIBA or PCR

• Adequate medical condition for general anesthesia

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from recent surgery

• At least 3 weeks since prior chemotherapy

• No prior high-dose therapy with autologous bone marrow transplantation

• No other concurrent chemotherapy

• No other concurrent treatment (e.g., surgery or radiotherapy)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Ovarian Cancer
• Teratoma
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• carboplatin

• ifosfamide

• paclitaxel

Procedure:
• autologous hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response (complete and partial)		2 year	No
Primary	Maximum tolerated dose of paclitaxel, carboplatin, and ifosfamide		2 year	Yes
Primary	Efficacy		2 year	No
Primary	Safety		2 year	Yes