Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
- Conditions
- Brain TumorsCentral Nervous System TumorsNeuroblastoma
- Interventions
- Biological: filgrastimProcedure: adjuvant therapyRadiation: radiation therapy
- Registration Number
- NCT00003203
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining carboplatin and vincristine with radiation therapy followed by adjuvant chemotherapy may kill more tumor cells.
PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed adjuvant chemotherapy in treating young patients who have newly diagnosed high-risk CNS embryonal tumors.
- Detailed Description
OBJECTIVES:
* Determine the feasible dose and duration of carboplatin combined with craniospinal and local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk CNS embryonal tumors (Phase I completed as of 11-25-03).
* Determine the feasibility of administering cyclophosphamide and vincristine with or without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these patients.
* Determine the overall and individual toxicity rates of this regimen in these patients.
* Determine the complete response rate in patients treated with this regimen.
* Obtain preliminary estimates of event-free survival of patients treated with this regimen.
* Determine the prognostic significance of enhancing tumor after completion of radiotherapy on event-free survival of these patients.
OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of 11-25-03.)
Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days a week for 6 weeks.
Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12 patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)
At 6 weeks after completion of radiotherapy, patients are assigned to arm II for adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)
* Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1 hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood counts recover.
* Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine IV on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on day 3 and continuing for at least 10 days until blood counts recover.
In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.
Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 168
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Newly diagnosed cerebral PNET with histologic verification filgrastim Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification vincristine sulfate Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification adjuvant therapy Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification radiation therapy Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification carboplatin Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification cyclophosphamide Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B). Newly diagnosed cerebral PNET with histologic verification cisplatin Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B).
- Primary Outcome Measures
Name Time Method Event Free Survival Length of study Minimum time to disease progression or recurrence, time to death for any reason, or time to occurrence of a second malignant neoplasm (SMN).
- Secondary Outcome Measures
Name Time Method Survival Length of study Time to death from any cause
Trial Locations
- Locations (38)
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
CCOP - Merit Care Hospital
🇺🇸Fargo, North Dakota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, 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 Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
Children's Hospital of Denver
🇺🇸Denver, Colorado, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, 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
University of Pennsylvania Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center
🇺🇸New York, New York, United States
Lineberger Comprehensive Cancer Center, UNC
🇺🇸Chapel Hill, North Carolina, United States
Vanderbilt Cancer Center
🇺🇸Nashville, Tennessee, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
IWK Grace Health Centre
🇨🇦Halifax, Nova Scotia, Canada