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Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor


Phase 3
3 Years
21 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

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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 PhiladelphiaPhiladelphia, Pennsylvania  19104
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Texas Children's Cancer Center and Hematology Service at Texas Children's HospitalHouston, Texas  77030-2399