Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: cisplatin (Drug); cyclophosphamide (Drug); filgrastim (Drug); lomustine (Drug); mesna (Drug); vincristine (Drug); low-LET electron therapy (Procedure); low-LET photon therapy (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: Children's Cancer Group

Official(s) and/or principal investigator(s):
Roger J. Packer, MD, Study Chair, Affiliation: Childrens Research Institute
Amar Gajjar, MD, Study Chair, Affiliation: St. Jude Children's Research Hospital

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.

Official title: A PHASE III PROSPECTIVE RANDOMIZED STUDY OF CRANIOSPINAL RADIOTHERAPY FOLLOWED BY ONE OF TWO ADJUVANT CHEMOTHERAPY REGIMENS (CCNU, CDDP, VCR OR CPM, CDDP, VCR) IN CHILDREN WITH NEWLY-DIAGNOSED AVERAGE-RISK MEDULLOBLASTOMA

Study design: Treatment, Randomized, Active Control

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.

Minimum age: 3 Years. Maximum age: 22 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Pathologically confirmed posterior fossa medulloblastoma (CCG diagnosis code 2041) Localized disease required, i. e.: No more than 1. 5 square centimeters of residual tumor on postoperative contrast-enhanced CT or MRI (preferably within 72 hours but no more than 14 days after surgery) No evidence of metastatic disease on pre- and postoperative MRI of spine (with dye enhancement) and lumbar cerebrospinal fluid (CSF) cytology within 3 days prior to surgery Cytologic analysis of ventricular CSF allowed only if medical contraindication to lumbar puncture and with approval of study chairperson Brain stem involvement eligible

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

University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan 00936-5067, Puerto Rico

Clinique de Pediatrie, Geneva 1211, Switzerland

British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada

Children's Hospital Los Angeles, Los Angeles, California 90027-0700, United States

Children's Hospital of Orange County, Orange, California 92668, United States

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States

Long Beach Memorial Medical Center, Long Beach, California 90806, 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

Via Christi Regional Medical Center, Wichita, Kansas 67214, United States

MBCCOP - LSU Medical Center, New Orleans, Louisiana 70112, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, 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

IWK Grace Health Centre, Halifax, Nova Scotia B3J 3G9, Canada

Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States

Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States

Ireland Cancer Center, Cleveland, Ohio 44106-5065, United States

Doernbecher Children's Hospital, Portland, Oregon 97201-3098, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Saint Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, 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

Cancer Center, University of Virginia HSC, Charlottesville, Virginia 22908, 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

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

Turgut M. Cerebellar mutism. J Neurosurg Pediatrics. 2008 Mar;1(3):262.

Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC; The 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):444-51.

Starting date: December 1996
Last updated: May 23, 2008