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

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00423852

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Cisplatin Paclitaxel Carboplatin Filgrastim Ifosfamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response (complete and partial) [ Designated as safety issue: No ]
Maximum tolerated dose of paclitaxel, carboplatin, and ifosfamide [ Designated as safety issue: Yes ]
Efficacy [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	68
Study Start Date:	August 2006
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

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.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study.

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
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	Recruiting
New York, New York, United States, 10065
Contact: Darren Feldman, MD 646-422-4491

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Darren Feldman, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Darren Feldman )
Study ID Numbers:	CDR0000522692, MSKCC-06077
Study First Received:	January 16, 2007
Last Updated:	May 20, 2009
ClinicalTrials.gov Identifier:	NCT00423852 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Gonadal Disorders
Seminoma
Urogenital Neoplasms
Ovarian Diseases
Central Nervous System Neoplasms
Genital Diseases, Female
Cisplatin
Neoplasms, Germ Cell and Embryonal
Ovarian Cancer
Alkylating Agents
Nervous System Neoplasms
Endocrine Gland Neoplasms
Extragonadal Germ Cell Tumor
Ovarian Neoplasms
Testicular Cancer

Genital Neoplasms, Female
Endocrine System Diseases
Antimitotic Agents
Testicular Neoplasms
Carboplatin
Recurrence
Ifosfamide
Paclitaxel
Mechlorethamine
Tubulin Modulators
Antineoplastic Agents, Alkylating
Nonseminomatous Germ Cell Tumor
Endocrinopathy
Antineoplastic Agents, Phytogenic
Teratoma

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Central Nervous System Neoplasms
Genital Diseases, Female
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Alkylating Agents
Nervous System Neoplasms
Endocrine Gland Neoplasms
Ovarian Neoplasms
Neoplasms by Histologic Type

Mitosis Modulators
Nervous System Diseases
Genital Neoplasms, Female
Endocrine System Diseases
Antimitotic Agents
Carboplatin
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Ifosfamide
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Teratoma

ClinicalTrials.gov processed this record on July 02, 2009