Clinical trial NCT00002875: Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma
Official title: Phase III Prospective Randomized Study of Craniospinal RT Followed by One of Two Adjuvant Chemotherapy Regimens (CCNU, CDDP, VCR OR CPM, CDDP, VCR) for Newly-Diagnosed Average Risk MedulloblastomaMEDULLOBLASTOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Tumors
Central Nervous System Tumors
Keywords: untreated childhood medulloblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Pediatric Oncology Group
First posted: 2004-05-24
Enrollment: 421
Sex: ALL
Minimum age (years): 3
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Event Free Survival
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Denver
country: United States
facility: Children's Hospital of Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Medical Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: Saint Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: Cancer Center, University of Virginia HSC
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: IWK Grace Health Centre
state: Nova Scotia
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
city: Geneva
country: Switzerland
facility: Clinique de Pediatrie
Study officials:
affiliation: Children's National Research Institute
name: Roger J. Packer, MD
role: STUDY_CHAIR
affiliation: St. Jude Children's Research Hospital
name: Amar Gajjar, MD
role: STUDY_CHAIR
References:
citation: Turgut M. Cerebellar mutism. J Neurosurg Pediatr. 2008 Mar;1(3):262. doi: 10.3171/PED/2008/1/3/262.
citation: 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.
citation: 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.
citation: 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.