High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

High-Dose Thiotepa With Autologous Stem Cell Rescue in Patients With Malignancies Refractory to Conventional Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003173
• Other study ID #: 97-089
• Secondary ID: P30CA008748MSKCC
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: March 6, 2013
• Start date: September 1997
• Est. completion date: May 2003

Study information

• Verified date: March 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose thiotepa plus peripheral stem cell transplantation in treating patients with refractory solid tumors.

Description:

OBJECTIVES:

• Evaluate the efficacy and toxicity of sequential cycles of high dose thiotepa with stem cell rescue and filgrastim in patients with malignancies refractory to conventional chemotherapy or for whom conventional therapy is not available.

• Evaluate the effectiveness of autologous stem cells in restoring hematopoiesis following high dose thiotepa.

OUTLINE: Patients are stratified by type of tumor (neuroectodermal CNS tumor vs non-neuroectodermal CNS tumor vs non-CNS small round blue cell tumor vs other non-CNS tumor).

Autologous stem cells are obtained prior to the administration of thiotepa. Patients who do not have peripheral blood stem cells available may undergo a bone marrow harvest instead. Thiotepa is administered as a 3 hour infusion daily for 3 consecutive days. Stem cells are reinfused approximately 72 hours following the completion of thiotepa. Filgrastim is administered the day following reinfusion of stem cells and continues until there is sufficient hematopoietic recovery.

The second course of thiotepa is administered 4 weeks following the first course in patients who have responding or stable disease, adequate stem cells, and no unacceptable toxicity. Patients receive a maximum of 2 courses.

PROJECTED ACCRUAL: Approximately 36 patients will be accrued for this study over 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2003
• Est. primary completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Malignant solid tumors

• Must have failed conventional treatment or for whom conventional therapy is not available

• Measurable disease by MRI or CT scan

• Intraocular retinoblastomas may be measured by direct visualization

• Germ cell tumors may be measured by tumor markers

• No known bone marrow involvement

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Lansky 60-100% for patients 16 and under

• Karnofsky 60-100% for patients over 16

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 75,000/mm^3

• If parameters not met, must have adequate stem cell yield

Hepatic:

• Bilirubin no greater than 1.5 times the upper limit of normal (ULN)

• SGOT and SGPT no greater than 2.5 times the ULN (unless liver involvement by tumor)

Renal:

• Creatinine within normal limits OR

• Creatinine clearance at least 70 mL/min

Cardiovascular:

• Fractional shortening greater than 28% on echocardiogram OR

• Ejection fraction at least 55% on RNCA prior to first cycle of thiotepa

Pulmonary:

• DLCO greater than 55% of predicted (only required if there is clinical evidence of pulmonary dysfunction)

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior bone marrow or peripheral blood stem cell rescue allowed

Chemotherapy:

• At least 4 weeks since prior chemotherapy if absolute neutrophil count is less than 1,000/mm^3 or platelet count is less than 75,000/mm^3, and recovered (i.e. adequate stem cells collected to predict hematopoietic recovery)

• No concurrent chemotherapy except for dexamethasone for antiedema effects

Endocrine therapy:

• No concurrent use of corticosteroids used solely as antiemetics

Radiotherapy:

• At least 4 weeks since radiotherapy if absolute neutrophil count is less than 1,000/mm^3 or platelet count is less than 75,000/mm^3, and recovered (i.e. adequate stem cells collected to predict hematopoietic recovery)

• No concurrent radiotherapy

Surgery:

• Not specified

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Ovarian Cancer
• Retinoblastoma
• Testicular Germ Cell Tumor
• Testicular Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Biological:
• filgrastim

Drug:
• thiotepa

Procedure:
• autologous bone marrow transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,