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Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma

This study has been completed.
Sponsor:
Collaborators:
Pediatric Oncology Group
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002875
First received: November 1, 1999
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Masking: Single Blind
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival [ Designated as safety issue: No ]

Enrollment: 421
Study Start Date: December 1996
Study Completion Date: January 2011
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   3 Years to 22 Years
Genders Eligible for Study:   Both
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002875

  Show 41 Study Locations
Sponsors and Collaborators
Children's Oncology Group
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
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002875     History of Changes
Other Study ID Numbers: A9961, CCG-A9961, POG-A9961, CDR0000065160
Study First Received: November 1, 1999
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on November 20, 2014