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 doctors to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Feasibility
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
Time frame: Up to 4 weeks after completion of study treatment
Maximal tolerated dose of thiotepa for consolidation therapy
The dose level will be assigned within 3 working days prior to beginning Consolidation.
Time frame: 9 weeks
Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV)
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.
Time frame: Up to 6 years
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
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Children's Hospital and Research Center Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
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Aurora, Colorado, United States
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