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
filgrastim
+ carboplatin
+ etoposide
Urogenital Diseases+17
+ Genital Diseases
+ Adnexal Diseases
Treatment Study
Summary
Study start date: January 1, 1994
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.108 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 15 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Memorial Sloan-Kettering Cancer Center
New York, United StatesOpen Memorial Sloan-Kettering Cancer Center in Google Maps