Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002875
• Collaborator: National Cancer Institute (NCI) (NIH), Pediatric Oncology Group (Other)
• Enrollment: 421
• Locations: 41
• Arms: 2
• Duration (Months): 169
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors; Central Nervous System Tumors	Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: lomustine; Drug: mesna; Drug: vincristine sulfate; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 421 participants
• Allocation: Randomized
• Masking: Single
• Primary Purpose: Treatment
• 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 Start Date: Dec 1, 1996
• Actual Primary Completion Date: Feb 1, 2006
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: filgrastim; Other Names: G-CSF Neupogen NSC-614629 ; Drug: cisplatin; Other Names: Platinol NSC-119875 ; Drug: cyclophosphamide; Other Names: Cytoxan NSC-26271 ; Drug: lomustine; Other Names: CCNU NSC-79037 ; Drug: mesna; Other Names: Mesnex NSC-113891 ; Drug: vincristine sulfate; Other Names: Oncovin NSC-67574 ; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy
Experimental: 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.	Biological: filgrastim; Other Names: G-CSF Neupogen NSC-614629 ; Drug: cisplatin; Other Names: Platinol NSC-119875 ; Drug: cyclophosphamide; Other Names: Cytoxan NSC-26271 ; Drug: mesna; Other Names: Mesnex NSC-113891 ; Drug: vincristine sulfate; Other Names: Oncovin NSC-67574 ; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy

Outcome Measures

Primary Outcome Measures

1. Event Free Survival []

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 22 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
3	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
4	Children's Hospital of Orange County	Orange	California	United States	92668
5	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
6	Children's Hospital of Denver	Denver	Colorado	United States	80218
7	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
8	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
9	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5265
10	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
11	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
12	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
13	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
14	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
15	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
16	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
17	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
18	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
19	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
20	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
21	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
22	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
23	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio	United States	45229-3039
24	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
25	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
26	Doernbecher Children's Hospital	Portland	Oregon	United States	97201-3098
27	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
28	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
29	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
30	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
31	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
32	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
33	Cancer Center, University of Virginia HSC	Charlottesville	Virginia	United States	22908
34	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
35	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
36	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
37	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
38	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
39	IWK Grace Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
40	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan		Puerto Rico	00936-5067
41	Clinique de Pediatrie	Geneva		Switzerland	1211

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)
• Pediatric Oncology Group

Investigators

• Study Chair: Roger J. Packer, MD, Children's National Research Institute
• Study Chair: Amar Gajjar, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00002875
• Other Study ID Numbers: A9961; CCG-A9961; POG-A9961; CDR0000065160
• First Posted: May 24, 2004
• Last Update Posted: Aug 1, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Children's Oncology Group: untreated childhood medulloblastoma
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Cyclophosphamide; Lomustine; Cisplatin; Vincristine

Study Results

No Results Posted as of Aug 1, 2014