Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
SECONDARY OBJECTIVES:
- To compare the effects of a computer-based training system specifically targeting
language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation)
with the current standard of care on reading decoding skills as measured by individual
academic testing.
- To monitor for treatment failure in the posterior fossa of patients whose tumor bed
receives a reduced volume of radiation.
- To correlate radiation dosimetry of target and normal tissues with rate and patterns of
failure and longitudinal measures of audiometric, endocrine and cognitive effects.
EXPLORATORY OBJECTIVES:
- To estimate the change in neuropsychological performance from the neuropsychology
assessment battery (intellect, academic achievement and cognitive ability) and examine
the relationship of these changes to risk group, age at diagnosis, and parent measures.
- To evaluate the differences between neurotoxicity in the average-risk patient group
with that in the high-risk group through qMRI, and fMRI.
- To develop or refine novel models relating impact of medulloblastoma therapy on
neurocognitive performance to quantitative and functional neuroimaging measures.
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk
(high-risk disease vs average-risk disease).
Patients in both strata undergo peripheral blood stem cell or bone marrow harvest.
- Stratum 1 (high-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy once daily 5 days a week
for 6 weeks.
- High-dose chemotherapy and autologous stem cell transplantation (SCT): Six weeks
after the completion of radiotherapy, patients receive high-dose chemotherapy
comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and
cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo autologous SCT
on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1
and continuing until blood counts recover. Patients receive vincristine IV on day
6. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional
courses in the absence of unacceptable toxicity.
- Stratum 2 (average-risk group):
- Radiotherapy: Patients undergo craniospinal radiotherapy as in stratum 1, but at a
lower dose.
- High-dose chemotherapy and autologous SCT: Patients receive high-dose
chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in
stratum 1.
Some patients undergo a neuropsychology assessment at baseline, before chemotherapy, and
then annually for 5 years.
After completion of study therapy, patients are followed every 3 months until month 30 (2.5
years) after diagnosis and then every 6 months until month 72 (6 years) after diagnosis.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Medulloblastoma
- Supratentorial primitive neuroectodermal tumor (PNET)
- PNET variants (ependymoblastoma, pineoblastoma, CNS neuroblastoma)
- Atypical teratoid rhabdoid tumor (ATRT)
- Definitive surgery for CNS tumor within the past 31 days
- Meets one of the following risk criteria:
- Average-risk disease
- Localized disease with no overt evidence of invasion beyond the posterior
fossa (or supratentorial compartment for PNET or ATRT) by intraoperative
observations of the neurosurgeon AND postoperative CT scan or MRI
- T4 disease eligible if all of the following are true:
- Gross total resection determined by intraoperative observations of the
neurosurgeon AND postoperative CT scan or MRI
- Residual tumor or imaging abnormality whose size is < 1.5 cm^2
- No evidence of CNS or extraneural metastasis by MRI of the spine (with
and without contrast agent) or CT-based myelogram AND by cytologic
examination of the lumbar cerebral spinal fluid (CSF) 14-28 days after
surgery
- Brain stem invasion allowed in the absence of residual tumor (tumor < 1.5
cm^2 by imaging)
- High-risk disease meeting one of the following criteria:
- Metastatic disease within the neuraxis (i.e., evidence of subarachnoid
dissemination by imaging and/or cytologic examination of CSF)
- Presence of residual disease > 1.5 cm^2 at the primary site after surgery
PATIENT CHARACTERISTICS:
Age
- 3 to 21 at diagnosis
Performance status
- Lansky 30-100% (< 10 years old)
- Karnofsky 30-100% (≥ 10 years old) (except for posterior fossa syndrome)
Life expectancy
- Not specified
Hematopoietic
- Hemoglobin > 8 g/dL
- WBC > 2,000/mm^3
- Absolute neutrophil count > 500/mm^3
- Platelet count > 50,000/mm^3
Hepatic
- ALT < 5 times normal
- Bilirubin < 3.0 mg/dL
Renal
- Creatinine < 2.0 mg/dL OR
- Creatinine clearance > 70 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Prior corticosteroid therapy allowed
Radiotherapy
- No prior radiotherapy
Surgery
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival in ERBB2-negative tumors compared to ERBB2-positive tumors
Outcome Description:
To assess the relationship between ERBB2 protein expression in tumors and progression-free survival for patients with medulloblastoma
Outcome Time Frame:
2 years after tumor cell analysis in 123 patients
Safety Issue:
No
Principal Investigator
Amar Gajjar, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
St. Jude Children's Research Hospital
Authority:
United States: Food and Drug Administration
Study ID:
SJMB03
NCT ID:
NCT00085202
Start Date:
August 2003
Completion Date:
September 2018
Related Keywords:
- Brain and Central Nervous System Tumors
- untreated childhood medulloblastoma
- untreated childhood supratentorial primitive neuroectodermal tumor
- childhood atypical teratoid/rhabdoid tumor
- untreated childhood pineoblastoma
- Medulloblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Rhabdoid Tumor
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital | Houston, Texas 77030-2399 |
