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Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

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ClinicalTrials.gov Identifier: NCT00002875
Recruitment Status : Completed
First Posted : May 24, 2004
Last Update Posted : August 1, 2014
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Pediatric Oncology Group
Information provided by (Responsible Party):
Children's Oncology Group

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 Type : Interventional  (Clinical Trial)
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 : December 1996
Actual Primary Completion Date : February 2006
Actual Study Completion Date : January 2011


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



Primary Outcome Measures :
  1. Event Free Survival


Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002875


  Show 41 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Pediatric Oncology Group
Investigators
Study Chair: Roger J. Packer, MD Children's Research Institute
Study Chair: Amar Gajjar, MD St. Jude Children's Research Hospital

Publications of Results:
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.

Other Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002875     History of Changes
Other Study ID Numbers: A9961
CCG-A9961 ( Other Identifier: Children's Cancer Group )
POG-A9961 ( Other Identifier: Pediatric Oncology Group )
CDR0000065160 ( Other Identifier: Clinical Trials.gov )
First Posted: May 24, 2004    Key Record Dates
Last Update Posted: August 1, 2014
Last Verified: July 2014

Keywords provided by Children's Oncology Group:
untreated childhood medulloblastoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Medulloblastoma
Neoplasms by Site
Neoplasms
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cisplatin
Cyclophosphamide
Vincristine
Lomustine
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents