Combination Chemotherapy in Treating Patients With Germ Cell Tumors That Have Not Responded to Previous Cisplatin

PHASE I/II TRIAL OF TAXOL, IFOSFAMIDE, AND CISPLATIN FOR CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH FAVORABLE PROGNOSTIC FEATURES

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy consisting of paclitaxel, cisplatin, and ifosfamide in treating patients who have ovarian or testicular germ cell tumors that are refractory to platinum-containing chemotherapy.

Study Overview

• Status: Completed
• Conditions: Testicular Germ Cell Tumor; Ovarian Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: paclitaxel; Biological: filgrastim; Drug: ifosfamide

Detailed Description

OBJECTIVES:

• Determine the toxicity and optimal dose of paclitaxel when combined with cisplatin and ifosfamide in patients with germ cell tumors with favorable prognostic features and resistance to cisplatin.
• Determine the efficacy of this regimen as salvage therapy in these patients.

OUTLINE: This is a dose escalation study of paclitaxel.

Patients receive paclitaxel IV continuously on day 1 and cisplatin IV over 20 minutes and ifosfamide IV over 30 minutes on days 2-6. Filgrastim (G-CSF) is administered subcutaneously (SC) on days 7-18 or until blood counts recover. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity. Additional patients receive paclitaxel at the MTD.

After completion of chemotherapy, some patients may undergo resection of residual masses.

PROJECTED ACCRUAL: A total of 18-43 patients will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven germ cell tumor that is resistant to a platinum-based chemotherapy regimen

• Active disease meeting 1 of the following conditions:

  • Measurable or evaluable disease
  • Elevated serum tumor markers (alpha-fetoprotein or human chorionic gonadotropin)
  • Unresectable residual disease after postchemotherapy surgery

• Favorable prognostic factors for achieving a complete response (CR) to cisplatin-based salvage therapy required, including all of the following:

  • No more than 1 prior regimen or 6 prior courses of cisplatin
  • Testis or ovarian germ cell primary site
  • Prior CR to cisplatin therapy
  • Incomplete response to first-line therapy that was based on either carboplatin or a suboptimal regimen of cisplatin

PATIENT CHARACTERISTICS:

Age:

• 15 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Not specified

Renal:

• Creatinine clearance greater than 50 mL/min
• Renal dysfunction due to ureteral obstruction by tumor allowed at the discretion of the principal investigator

Cardiovascular:

• If history of significant cardiac disease, evaluation and clearance by a cardiologist required prior to entry

Other:

• No active infection not well controlled on antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior paclitaxel or ifosfamide
• At least 3 weeks since prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics
• Recovered from recent surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 1994
• Primary Completion (Actual): January 1, 2003
• Study Completion (Actual): January 1, 2003

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: September 17, 2003
• First Posted (Estimate): September 18, 2003

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: recurrent ovarian germ cell tumor; recurrent malignant testicular germ cell tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin; Ifosfamide
• Other Study ID Numbers: 94-012; CDR0000063452 (Registry Identifier: PDQ (Physician Data Query)); NCI-V94-0408