Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma
- Conditions
- Central Nervous System TumorsBrain Tumors
- Interventions
- Biological: filgrastimRadiation: low-LET electron therapyRadiation: 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
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Regimen A vincristine sulfate Following 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 A low-LET electron therapy Following 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 A low-LET photon therapy Following 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 B low-LET electron therapy Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen A filgrastim Following 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 B filgrastim Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen B vincristine sulfate Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen B low-LET photon therapy Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen A cyclophosphamide Following 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 A lomustine Following 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 A cisplatin Following 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 A mesna Following 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 B cisplatin Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen B cyclophosphamide Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Regimen B mesna Following 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
Name Time Method Event Free Survival
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (41)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
Children's Hospital of Denver
🇺🇸Denver, Colorado, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, 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
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
MBCCOP - LSU Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Lineberger Comprehensive Cancer Center, UNC
🇺🇸Chapel Hill, North Carolina, United States
Children's Hospital Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Vanderbilt Cancer Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Cancer Center, University of Virginia HSC
🇺🇸Charlottesville, Virginia, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
IWK Grace Health Centre
🇨🇦Halifax, Nova Scotia, Canada
University of Puerto Rico School of Medicine Medical Sciences Campus
🇵🇷San Juan, Puerto Rico
Clinique de Pediatrie
🇨ðŸ‡Geneva, Switzerland
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States