Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 316 patients (158 per treatment arm) will be accrued for this study within 4 years.

Official Title
-----------------
A Prospective Randomised Controlled Trial Of Hyperfractionated Versus Conventionally Fractionated Radiotherapy In Standard Risk Medulloblastoma

Conditions
-----------------
Brain and Central Nervous System Tumors

Intervention / Treatment
-----------------
* Drug: cisplatin
* Drug: lomustine
* Drug: vincristine sulfate
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: lomustine|nan|
|Drug: vincristine sulfate|nan|
|Procedure: adjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of event-free survival at 3 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of overall survival |  |  | 
| Comparison of the pattern of relapse (i.e., local relapse [tumor bed and posterior fossa outside tumor bed]) |  |  | 
| Comparison of late sequelae, in terms of health status, quality of life, hearing loss, and endocrine deficiencies |  |  | 
| Toxicity of neurosurgery |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
untreated childhood medulloblastoma