RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy in different ways with combination chemotherapy may kill any remaining tumor cells following surgery. It is not yet known which radiation therapy regimen combined with combination chemotherapy is more effective in treating medulloblastoma.

PURPOSE: Randomized phase III trial to compare different radiation therapy regimens plus combination chemotherapy in treating children who have undergone surgery for medulloblastoma.

Condition	Treatment or Intervention	Phase
untreated childhood medulloblastoma	Drug: cisplatin  Drug: lomustine  Drug: vincristine  Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the event-free survival rate in pediatric patients with standard-risk medulloblastoma treated with conventional vs hyperfractionated radiotherapy and vincristine followed by maintenance with cisplatin, lomustine, and vincristine.
• Compare the overall survival of patients treated with these regimens.
• Compare the pattern of relapse, especially local relapse (tumor bed or posterior fossa outside tumor bed), in patients treated with these regimens.
• Determine the toxicity of surgery and whether there are identifiable factors that correlate with toxicity in these patients.
• Determine the impact of any surgical complications on commencement of adjuvant therapy and event-free survival of these patients.
• Compare late sequelae, in terms of health status, endocrine deficiencies, and hearing loss, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to country. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 28-40 days after surgical resection, patients undergo conventional fractionated radiotherapy once daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine IV once weekly for 8 weeks.
• Arm II: Beginning as in arm I, patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine as in arm I.
• Maintenance chemotherapy:Six weeks after completion of radiotherapy, all patients receive cisplatin IV over 6 hours and oral lomustine on day 1 and vincristine IV on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 courses. Patients are followed at least every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 316 patients (158 per treatment arm) will be accrued for this study within 4 years.

Ages Eligible for Study:  3 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed medulloblastoma, including the following variants:
• Classic
• Nodular/desmoplastic
• Large cell
• Melanotic
• Medullomyoblastoma
• Prior total or subtotal surgical removal of tumor within the past 28-40 days
• No more than 1.5 cm^2 residual tumor by early postoperative MRI or CT scan
• No brainstem or supratentorial primitive neuroectodermal tumor
• No atypical teratoid rhabdoid tumor
• No known predisposition to medulloblastoma (e.g., Gorlin's syndrome)
• No CNS metastasis (supratentorial, arachnoid of the posterior fossa, or craniospinal axis) by MRI
• No clinical evidence of metastasis outside the CNS
• No tumor cells in lumbar cerebrospinal fluid by cytospin

PATIENT CHARACTERISTICS: Age

• 3 to 21

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Hematological function less than CTC grade 2

Hepatic

• Liver function less than CTC grade 2

Renal

• Renal function less than CTC grade 2

Other

• Not pregnant
• Fertile patients must use effective contraception
• Able to receive radiotherapy twice daily
• Vital functions within age-appropriate normal range
• Audiological function less than CTC grade 2
• No medical contraindication to radiotherapy or chemotherapy

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Concurrent dexamethasone as an antiemetic allowed, provided all other therapies have failed

Radiotherapy

• No concurrent cobalt irradiation

Surgery

• See Disease Characteristics

Other

• No prior treatment for brain tumor or any other malignancy

Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
France
      Institut Curie - Section Medicale, Paris,  75248,  France; Recruiting
Germany
      Universitaets - Kinderklinik Wuerzburg, Wuerzburg,  D-97080,  Germany; Recruiting
      Universitaetsklinikum Tuebingen, Tuebingen,  D-72076,  Germany; Recruiting
Italy
      Ospedale Infantile Regina Margherita, Turin,  10126,  Italy; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
Spain
      Hospital de Cruces, Vizcaya,  48,  Spain; Recruiting
Sweden
      Ostra Sjukhuset, GOTHENBURG,  41685,  Sweden; Recruiting
United Kingdom, England
      Royal Liverpool Children's Hospital, Alder Hey, Liverpool,  England,  L12 2AP,  United Kingdom; Recruiting

Study chairs or principal investigators

Brigitta Lannering, MD, PhD,  Study Chair,  Ostra Sjukhuset   

Study ID Numbers:  CDR0000269521; SIOP-PNET-4; EU-20244; NCT00053872
Record last reviewed:  February 2003
Last Updated:  December 6, 2004
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00053872
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08