Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

NCT ID: NCT00053872

Last Updated: 2014-06-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

cisplatin

Intervention Type: DRUG

lomustine

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leicester

OTHER

Sponsor Role: lead

Principal Investigators

Brigitta Lannering, MD, PhD

Role: STUDY_CHAIR

Ostra Sjukhuset

Locations

U.Z. Gasthuisberg

Leuven, , Belgium

Institut Curie Hopital

Paris, , France

Universitaets - Kinderklinik Wuerzburg

Würzburg, , Germany

Ospedale Infantile Regina Margherita

Turin, , Italy

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, , Netherlands

Hospital de Cruces

Vizcaya, , Spain

Ostra Sjukhuset

Gothenburg, , Sweden

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Countries

Belgium; France; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

Other Identifiers

SIOP-PNET-4

Identifier Type: -

Identifier Source: secondary_id

EU-20244

Identifier Type: -

Identifier Source: secondary_id

UKCCSG-CNS-2003-05

Identifier Type: -

Identifier Source: secondary_id

CDR0000269521

Identifier Type: -

Identifier Source: org_study_id