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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


Phase 1/Phase 2
15 Years
N/A
Not Enrolling
Both
Extragonadal Germ Cell Tumor, Ovarian Cancer, Testicular Germ Cell Tumor

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Trial Information

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


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.

Inclusion 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Gnanamba V. Kondagunta, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

93-162

NCT ID:

NCT00002558

Start Date:

January 1994

Completion Date:

April 2009

Related Keywords:

  • Extragonadal Germ Cell Tumor
  • Ovarian Cancer
  • Testicular Germ Cell Tumor
  • recurrent malignant testicular germ cell tumor
  • recurrent ovarian germ cell tumor
  • extragonadal germ cell tumor
  • Ovarian Neoplasms
  • Neoplasms, Germ Cell and Embryonal

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021