Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

NCT ID: NCT00002875

Last Updated: 2014-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

421 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-12-31

Study Completion Date

2011-01-31

Brief Summary

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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

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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.

Conditions

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Brain Tumors Central Nervous System Tumors

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Study Groups

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Regimen A

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.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

lomustine

Intervention Type DRUG

mesna

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Regimen B

Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

mesna

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Interventions

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filgrastim

Intervention Type BIOLOGICAL

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

lomustine

Intervention Type DRUG

mesna

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Other Intervention Names

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G-CSF Neupogen NSC-614629 Platinol NSC-119875 Cytoxan NSC-26271 CCNU NSC-79037 Mesnex NSC-113891 Oncovin NSC-67574

Eligibility Criteria

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Inclusion Criteria

PATIENT CHARACTERISTICS: Age: 3 to 21 at diagnosis Performance status: Not specified Hematopoietic: ANC greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: Bilirubin less than 1.5 mg/dL ALT less than 1.5 times normal Renal: Nuclear glomerular filtration rate or creatinine clearance greater than 70 mL/min per 1.73 square meters

PRIOR CONCURRENT THERAPY: No prior radiotherapy or chemotherapy (other than corticosteroids) No more than 31 days since definitive surgery
Minimum Eligible Age

3 Years

Maximum Eligible Age

22 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Pediatric Oncology Group

OTHER

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roger J. Packer, MD

Role: STUDY_CHAIR

Children's National Research Institute

Amar Gajjar, MD

Role: STUDY_CHAIR

St. Jude Children's Research Hospital

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Children's Hospital of Denver

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Cancer Center, University of Virginia HSC

Charlottesville, Virginia, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Grace Health Centre

Halifax, Nova Scotia, Canada

Site Status

University of Puerto Rico School of Medicine Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Clinique de Pediatrie

Geneva, , Switzerland

Site Status

Countries

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United States Australia Canada Puerto Rico Switzerland

References

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Turgut M. Cerebellar mutism. J Neurosurg Pediatr. 2008 Mar;1(3):262. doi: 10.3171/PED/2008/1/3/262.

Reference Type BACKGROUND
PMID: 18352776 (View on PubMed)

Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC; Children's Oncology Group. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. J Neurosurg. 2006 Dec;105(6 Suppl):444-51. doi: 10.3171/ped.2006.105.6.444.

Reference Type BACKGROUND
PMID: 17184075 (View on PubMed)

Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. doi: 10.1200/JCO.2006.06.4980.

Reference Type RESULT
PMID: 16943538 (View on PubMed)

Packer RJ, Gajjar A, Vezina G, et al.: 2340 cGy of craniospinal radiotherapy (CSRT) plus chemotherapy for children with "average-risk" medulloblastoma (MB): a prospective randomized Children's Oncology Group study (A9961). [Abstract] Neuro-Oncology 6 (4): TP-06, 387, 2004.

Reference Type RESULT

Other Identifiers

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CCG-A9961

Identifier Type: OTHER

Identifier Source: secondary_id

POG-A9961

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000065160

Identifier Type: OTHER

Identifier Source: secondary_id

A9961

Identifier Type: -

Identifier Source: org_study_id

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