Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00002558
First received: November 1, 1999
Last updated: April 11, 2016
Last verified: April 2016
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed.

The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support.

PURPOSE: The purpose of this study is to determine the effects of an intensive sequence of chemotherapy drugs in patients with metastatic germ cell cancer. All of these chemotherapy drugs are known to be active in this disease.


Condition Intervention Phase
Extragonadal Germ Cell Tumor
Ovarian Cancer
Testicular Germ Cell Tumor
Biological: filgrastim
Drug: carboplatin
Drug: etoposide
Drug: ifosfamide
Drug: paclitaxel
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 TAXOL/IFOSFAMIDE AND DOSEINTENSIVE CARBOPLATIN/ETOPOSIDE WITH STEM CELL SUPPORT IN CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Objective Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy}


Enrollment: 108
Study Start Date: January 1994
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: chemotherapy administered with G-CSF and PBSC support
The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support.
Biological: filgrastim Drug: carboplatin Drug: etoposide Drug: ifosfamide Drug: paclitaxel Procedure: peripheral blood stem cell transplantation

Detailed Description:

OBJECTIVES:

  • Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin.
  • Determine the efficacy of this regimen as salvage therapy in these patients.
  • Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients.
  • Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients.

OUTLINE: This is a dose escalation study of carboplatin.

  • Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy.
  • Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM.

During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin 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.

After completion of parts A and B, some patients may undergo resection of residual masses.

  Eligibility

Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Male/Female with histologically confirmed GCT with review by the Department of Pathology at this center.
  • Patients with advanced GCT, including patients with:

measurable or evaluable disease,

  • patients with only elevated serum tumor markers (AFP and/or HCG), or
  • patients with known residual disease after postchemotherapy surgery. Eligible patients must have established clinical resistance to cisplatin by their failure to achieve a durable CR to a cisplatin-based regimen.
  • Prior treatment limited to ≤ 6 prior cycles (≤ four cycles preferred) of cisplatin. (GROUP A)
  • Prior therapy > 6 cycles of cisplatin. (GROUP B)
  • Therapy must have been discontinued at least 3 weeks before entry onto protocol.
  • Patients must have one or more unfavorable prognostic factors for achieving a CR to cisplatin-based salvage therapy. These are:
  • Extragonadal primary site.
  • Testis/ovarian primary site with the best response of an IR to first-line therapy, or a partial response with normal tumor markers of six months or less in duration.
  • Prior treatment with ifosfamide-containing therapy
  • General medical condition sufficient to allow for general anesthesia at the time of pheresis catheter placement.
  • Patients must have negative serology for Human Immunodeficiency Virus.
  • Laboratory criteria for protocol entry:

WBC ≥ 3000/ul Platelets 3 100,000/ul Cr Clearance > 50 cc/min*

* (unless renal dysfunction is due to tumor obstructing the ureters in which case eligibility will be determined by the Principal Investigator).

  • Age ≥ 15 years.
  • Signed informed consent.

Exclusion Criteria:

  • Presence of active infection
  • Concurrent treatment with chemotherapy or
  • Inability to comply with the treatment protocol or to undergo the specified follow-up tests for safety or effectiveness.
  • Prior high-dose therapy with AuBMT.
  • Patients must have recovered from recent surgery.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002558

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
National Cancer Institute (NCI)
Investigators
Study Chair: Gnanamba V. Kondagunta, MD Memorial Sloan Kettering Cancer Center
  More Information

Publications:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00002558     History of Changes
Other Study ID Numbers: 93-162  P30CA008748  MSKCC-93162  NCI-V94-0407 
Study First Received: November 1, 1999
Results First Received: December 21, 2015
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan Kettering Cancer Center:
recurrent malignant testicular germ cell tumor
recurrent ovarian germ cell tumor
extragonadal germ cell tumor

Additional relevant MeSH terms:
Neoplasms
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Paclitaxel
Etoposide
Etoposide phosphate
Isophosphamide mustard
Carboplatin
Ifosfamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 28, 2016