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Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

Phase 3
Completed
Conditions
Central Nervous System Tumors
Brain Tumors
Interventions
Biological: filgrastim
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Registration Number
NCT00002875
Lead Sponsor
Children's Oncology Group
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. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective when combined with radiation therapy for treating medulloblastoma.

PURPOSE: Randomized phase III trial to compare two combination chemotherapy treatments plus radiation therapy in treating children with newly diagnosed medulloblastoma.

Detailed Description

OBJECTIVES: I. Assess whether a cyclophosphamide-containing combination chemotherapy regimen increases progression-free survival compared to a lomustine-containing regimen in children with newly diagnosed, average-risk medulloblastoma. II. Determine progression-free and overall survival of children treated with craniospinal radiotherapy and local boost radiotherapy for a total dose of 5580 cGy followed by adjuvant lomustine/cisplatin/vincristine vs. cyclophosphamide/cisplatin/vincristine. III. Determine the long-term neurocognitive, endocrinologic, and cardiopulmonary sequelae associated with craniospinal radiotherapy, local boost radiotherapy, and adjuvant chemotherapy in these children, and determine whether replacement of lomustine with cyclophosphamide alters the incidence and degree of sequelae. IV. Determine whether cellular and biologic parameters, including tumor molecular genetic analysis, DNA ploidy, mitotic activity markers, and immunohistochemical analysis, are correlated with progression-free survival, overall survival, and patterns of disease relapse in these patients. V. Evaluate the utility of routine magnetic resonance imaging surveillance studies of the head and spine in detecting subclinical recurrent disease.

OUTLINE: This is a randomized study. Patients are stratified by participating institution. Following surgery, patients are randomized to one of two groups. The first group receives craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine/cisplatin every 6 weeks for a total of 8 courses. The second group receives craniospinal irradiation plus vincristine as above, followed by adjuvant cyclophosphamide/vincristine/cisplatin every 6 weeks for a total of 8 courses. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually.

PROJECTED ACCRUAL: It is anticipated that 240-300 patients will be entered over 4 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
421
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Regimen Avincristine sulfateFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen Alow-LET electron therapyFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen Alow-LET photon therapyFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen Blow-LET electron therapyFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen AfilgrastimFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen BfilgrastimFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen Bvincristine sulfateFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen Blow-LET photon therapyFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen AcyclophosphamideFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen AlomustineFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen AcisplatinFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen AmesnaFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen BcisplatinFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen BcyclophosphamideFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Regimen BmesnaFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.
Primary Outcome Measures
NameTimeMethod
Event Free Survival
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (41)

Long Beach Memorial Medical Center

🇺🇸

Long Beach, California, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

🇺🇸

Los Angeles, California, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

UCSF Cancer Center and Cancer Research Institute

🇺🇸

San Francisco, California, United States

Children's Hospital of Denver

🇺🇸

Denver, Colorado, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

University of Chicago Cancer Research Center

🇺🇸

Chicago, Illinois, United States

Indiana University Cancer Center

🇺🇸

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Scroll for more (31 remaining)
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States

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