Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support
3 Years
21 Years
Both
Brain and Central Nervous System Tumors, Neuroblastoma
Trial Information
Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support
OBJECTIVES:
- Determine the safety of postradiotherapy high-dose consolidation chemotherapy with
peripheral blood stem cell (PBSC) support in patients with high-risk primitive
neuroectodermal tumors.
- Determine the safety of delaying radiotherapy by approximately one month in these
patients.
- Determine the maximum tolerated dose of thiotepa in these patients.
- Determine the toxic effects of intensive chemotherapy with PBSC support in these
patients.
- Assess the time to hematopoietic recovery after PBSC infusion when intensive
chemotherapy is used after craniospinal radiotherapy in these patients.
- Determine the overall and event-free survival of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of thiotepa during consolidation therapy.
- Induction: Within 31 days of initial surgery, patients receive induction therapy
comprising vincristine IV on day 0, cyclophosphamide IV over 2 hours on days 0 and 1,
and filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing for at
least 7-10 days. Peripheral blood stem cells (PBSC) are then collected.
- Chemoradiotherapy: After blood cell counts recover, and within 28 days of starting
induction, patients begin chemoradiotherapy. Patients receive vincristine IV once
weekly for 8 doses. Radiotherapy is administered 5 days a week, for 6 weeks, beginning
within the same week as the start of vincristine.
- Consolidation: Therapy begins 4-6 weeks after the last radiation treatment in the
absence of disease progression. The first and third course are the same and comprise
vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, thiotepa IV over 3
hours on days 2-4, and G-CSF SC daily beginning on day 7. PBSC are reinfused on day 7.
The second course comprises vincristine IV on day 0, carboplatin IV over 1 hour on days
0 and 1, cyclophosphamide IV over 2 hours on days 2 and 3, and G-CSF SC daily beginning
on day 5. PBSC are reinfused on day 5. Each course lasts 21 days.
For consolidation therapy, cohorts of 6-12 patients each receive escalating doses of
thiotepa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose at which no more than 2 of 12 patients experience dose-limiting toxicity.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.
PROJECTED ACCRUAL: A total of 24-56 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven primitive neuroectodermal tumor (PNET) of one of the following
types:
- Atypical teratoid/rhabdoid tumor
- Medulloblastoma
- Desmoplastic medulloblastoma
- Ependymoblastoma
- Medullomyoblastoma
- Spongioblastoma
- Spongioblastoma polare
- Primitive polar spongioblastoma
- Medulloepithelioma
- Neuroblastoma
- Pineoblastoma
- Posterior fossa PNET must be M1-3 or M0 with greater than 1.5 cm2 residual disease
- Nonposterior fossa PNET and other types must be M0-3
- If M3, must show clear evidence of tumor on MRI
- No marrow involvement or other extraneural metastases
- No M4 disease
- No cord compression requiring emergency radiotherapy
PATIENT CHARACTERISTICS:
Age:
- 3 to 21
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 150,000/mm^3 (no platelet transfusions)
- Hemoglobin at least 10 g/dL (red blood cell transfusions allowed)
Hepatic:
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- AST or ALT less than 2.5 times ULN
Renal:
- Creatinine clearance or glomerular filtration rate at least 70 mL/min
Cardiovascular:
- Shortening fraction greater than 27% by echocardiogram OR
- Ejection fraction greater than 47% by MUGA
Pulmonary:
- FEV_1/FVC greater than 60% except for children who:
- Are uncooperative
- Have no dypsnea at rest
- Have no exercise intolerance
- Have pulse oximetry greater than 94% on room air
Other:
- Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- Steroids for increased intracranial pressure allowed
Radiotherapy:
- See Disease Characteristics
- No prior urgent radiotherapy
Surgery:
- Not specified
Other:
- No prior therapy for tumor
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
H. Stacy Nicholson, MD, MPH
Investigator Role:
Study Chair
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000067006
NCT ID:
NCT00003846
Start Date:
July 1999
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- Neuroblastoma
- regional neuroblastoma
- disseminated neuroblastoma
- stage 4S neuroblastoma
- untreated childhood supratentorial primitive neuroectodermal tumor
- untreated childhood medulloblastoma
- newly diagnosed childhood ependymoma
- Nervous System Neoplasms
- Neuroblastoma
- Central Nervous System Neoplasms
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York 10016 |
| Oregon Cancer Center at Oregon Health Sciences University | Portland, Oregon 97201-3098 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's Hospital of Denver | Denver, Colorado 80218 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Hospital Medical Center - Cincinnati | Cincinnati, Ohio 45229-3039 |
| Children's Hospital of Columbus | Columbus, Ohio 43205-2696 |
