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A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Phase 3
3 Years
21 Years
Open (Enrolling)
Brain Tumor, Central Nervous System Tumor

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Trial Information

A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial



- Compare event-free and overall survival of pediatric patients (3 to 7 years of age)
with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs
reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost
radiotherapy in combination with chemotherapy comprising vincristine, cisplatin,
lomustine, and cyclophosphamide.

- Compare event-free and overall survival of these patients (8 to 21 years of age)
treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor
bed boost radiotherapy in combination with this chemotherapy regimen.


- Compare patterns of failure in patients treated with these regimens.

- Compare the cognitive, auditory, and endocrinologic effects of these regimens in these

- Compare the audiologic and endocrinologic toxicity from these regimens in these

- Develop an optimal gene expression medulloblastoma outcome predictor.

- Assess quality of life and functional status in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days
1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine
IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3
to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old
are assigned to arm II.

- Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26,
29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22,
29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of
age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old
are assigned to arm II.

- Radiotherapy (first randomization):

- Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost.

- Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost.
All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III
and IV).

- Radiotherapy boost (second randomization):

- Arm III: Patients will undergo radiotherapy boost to the entire posterior

- Arm IV: Patients will undergo radiotherapy boost to the tumor bed only.

- Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy,
patients receive 2 different regimens of maintenance chemotherapy for a total of 9
courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in
regimen B is 4 weeks (28 days) in duration.

- Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and
cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of
weeks 11, 17, 27, 33, 43, and 49.

- Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour
on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years
after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.

Inclusion Criteria


- Histologically confirmed medulloblastoma located in the posterior fossa

- Standard-risk disease

- Minimal volume, non-disseminated disease, defined by the following:

- Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days
after surgery

- No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed
by both of the following:

- Enhanced MRI of the spine within 5 days before surgery OR within 28 days
after surgery

- Negative cytological examination of CSF after surgery, but before study

- Brain stem involvement allowed



- 3 to 21 at diagnosis

Performance status

- Karnofsky 50-100% (> 16 years of age) OR

- Lansky 30-100% (≤ 16 years of age)

Life expectancy

- Not specified


- Absolute neutrophil count > 1,500/mm^3

- Platelet count > 100,000/mm^3 (transfusion independent)

- Hemoglobin > 10 g/dL (transfusions allowed)


- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST or ALT < 1.5 times ULN


- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


Biologic therapy

- Not specified


- No prior chemotherapy

Endocrine therapy

- Prior corticosteroids allowed


- No prior radiotherapy


- See Disease Characteristics

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to event-free survival (EFS)

Outcome Description:

Time-to-event for radiation therapy question will be based on logrank test. Interim monitoring for each study question will be based on the Lan-Demets criterion, with spending function αt. The time point for 100% information is defined as two years after the last patient has enrolled. Information expended will be computed based on the current available follow-up, using the parametric cure model for A9961.

Outcome Time Frame:

Time from study entry to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 3 years

Safety Issue:


Principal Investigator

Jeff M. Michalski, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University Siteman Cancer Center


United States: Federal Government

Study ID:




Start Date:

April 2004

Completion Date:

Related Keywords:

  • Brain Tumor
  • Central Nervous System Tumor
  • untreated childhood medulloblastoma
  • Brain Neoplasms
  • Medulloblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



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