An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors
- 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
- 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
- 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
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
- 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.
Primary Purpose: Treatment
Regina Jakacki, MD
Children's Hospital of Pittsburgh of UPMC
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|
|Lineberger Comprehensive Cancer Center, UNC||Chapel Hill, North Carolina 27599-7295|
|Ireland Cancer Center||Cleveland, Ohio 44106-5065|
|University of Pennsylvania Cancer Center||Philadelphia, Pennsylvania 19104|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|CCOP - Kalamazoo||Kalamazoo, Michigan 49007-3731|
|Vanderbilt Cancer Center||Nashville, Tennessee 37232-6838|
|CCOP - Merit Care Hospital||Fargo, North Dakota 58122|
|NYU School of Medicine's Kaplan Comprehensive Cancer Center||New York, New York 10016|
|Huntsman Cancer Institute||Salt Lake City, Utah 84112|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Herbert Irving Comprehensive Cancer Center||New York, New York 10032|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Long Beach Memorial Medical Center||Long Beach, California 90806|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's Hospital of Denver||Denver, Colorado 80218|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Mercy Hospital||Kansas City, Missouri 64108|
|St. Joseph's Hospital and Medical Center||Paterson, New Jersey 07503|
|Children's Hospital Medical Center - Cincinnati||Cincinnati, Ohio 45229-3039|
|Children's Hospital of Columbus||Columbus, Ohio 43205-2696|
|Doernbecher Children's Hospital||Portland, Oregon 97201-3098|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|