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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00423852
First received: January 16, 2007
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Ovarian Cancer
Teratoma
Testicular Germ Cell Tumor
Biological: filgrastim
Drug: carboplatin
Drug: ifosfamide
Drug: paclitaxel
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Response (complete and partial) [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Maximum tolerated dose of paclitaxel, carboplatin, and ifosfamide [ Time Frame: 2 year ] [ Designated as safety issue: Yes ]
  • Efficacy [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 2 year ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: August 2006
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423852

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Darren Feldman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00423852     History of Changes
Other Study ID Numbers: 06-077, MSKCC-06077
Study First Received: January 16, 2007
Last Updated: February 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent ovarian germ cell tumor
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent malignant testicular germ cell tumor
adult central nervous system germ cell tumor
stage III malignant testicular germ cell tumor
stage II malignant testicular germ cell tumor
recurrent extragonadal non-seminomatous germ cell tumor
recurrent extragonadal seminoma
stage III extragonadal non-seminomatous germ cell tumor
stage III extragonadal seminoma
stage IV extragonadal non-seminomatous germ cell tumor
stage IV extragonadal seminoma
recurrent extragonadal germ cell tumor
adult teratoma
testicular immature teratoma
testicular mature teratoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Ovarian Neoplasms
Teratoma
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Site
Neoplasms
Nervous System Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Isophosphamide mustard
Cisplatin
Ifosfamide
Carboplatin
Paclitaxel
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on April 23, 2014