Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain Tumors; Central Nervous System Tumors; Neuroblastoma
Intervention: filgrastim (Biological); carboplatin (Drug); cisplatin (Drug); cyclophosphamide (Drug); vincristine sulfate (Drug); adjuvant therapy (Procedure); radiation therapy (Radiation)
Phase: Phase 2
Status: Completed
Sponsored by: Children's Oncology Group Official(s) and/or principal investigator(s): Regina Jakacki, MD, Study Chair, Affiliation: Children's Hospital of Pittsburgh of UPMC
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.
Clinical Details
Official title: 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
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Event Free Survival
Secondary outcome: Survival
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.
Eligibility
Minimum age: 3 Years.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically proven high-risk CNS embryonal tumors, including:
- Primitive neuroectodermal tumors
- Atypical teratoid/rhabdoid tumor
- Medulloblastoma
- Desmoplastic medulloblastoma
- Ependymoblastoma
- Medullomyoblastoma
- Spongioblastoma
- Spongioblastoma polare
- Primitive polar spongioblastoma
- Neuroepitheliomatous neoplasms
- Medulloepithelioma
- Neuroblastoma
- Pineoblastoma
- No bone marrow involvement or bone metastases
- No M4 disease
- M3 disease must have evidence of tumor on spinal MRI
PATIENT CHARACTERISTICS:
Age:
- 3 to 21 at diagnosis
Performance status:
- Not specified
Life expectancy:
- At least 8 weeks
Hematopoietic:
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count at least 100,000/mm^3 (transfusion independent)
- Hemoglobin at least 10. 0 g/dL (packed red blood cell transfusions allowed)
Hepatic:
- Bilirubin less than 1. 5 mg/dL
- SGOT/SGPT less than 2. 5 times normal
Renal:
- Creatinine less than 1. 5 times upper limit of normal OR
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy
Surgery:
- Prior definitive surgery allowed
Locations and Contacts
British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada
Long Beach Memorial Medical Center, Long Beach, California 90806, United States
Children's Hospital Los Angeles, Los Angeles, California 90027-0700, United States
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States
Children's Hospital of Orange County, Orange, California 92668, United States
UCSF Cancer Center and Cancer Research Institute, San Francisco, California 94115-0128, United States
Children's Hospital of Denver, Denver, Colorado 80218, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5265, United States
University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
University of Nebraska Medical Center, Omaha, Nebraska 68198-3330, United States
St. Joseph's Hospital and Medical Center, Paterson, New Jersey 07503, United States
Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York 10016, United States
Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States
CCOP - Merit Care Hospital, Fargo, North Dakota 58122, United States
IWK Grace Health Centre, Halifax, Nova Scotia B3J 3G9, Canada
Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States
Ireland Cancer Center, Cleveland, Ohio 44106-5065, United States
Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States
Doernbecher Children's Hospital, Portland, Oregon 97201-3098, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States
University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Vanderbilt Cancer Center, Nashville, Tennessee 37232-6838, United States
University of Texas - MD Anderson Cancer Center, Houston, Texas 77030, United States
Huntsman Cancer Institute, Salt Lake City, Utah 84132, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 1998
Last updated: August 22, 2013
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