Primary Outcome Measures:
- Feasibility [ Time Frame: Up to 4 weeks after completion of study treatment ]
Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates
- Maximal tolerated dose of thiotepa for consolidation therapy [ Time Frame: 9 weeks ]
The dose level will be assigned within 3 working days prior to beginning Consolidation.
- Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV) [ Time Frame: Up to 6 years ]
Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.
Secondary Outcome Measures:
- Event Free Survival [ Time Frame: From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up ]
OBJECTIVES:
- Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
- Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
- Assess the feasibility of harvesting PBSCs in these patients.
- Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
Patients undergo surgery for diagnosis and maximal tumor resection.
Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.
Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.
PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.
Show 71 Study Locations