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Chemotherapy and Radiation Therapy After Surgery in Treating Children With Newly Diagnosed Astrocytoma, Glioblastoma Multiforme, Gliosarcoma, or Diffuse Intrinsic Pontine Glioma
This study has been completed.

First Received on January 4, 2002.   Last Updated on February 26, 2011   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00028795
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy together with radiation therapy after surgery followed by chemotherapy alone works in children with newly diagnosed astrocytoma, glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Procedure: adjuvant therapy
Radiation: radiation therapy
Phase II

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase II Study of Temozolomide in the Treatment of Children With High Grade Glioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Improved outcome [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE v. 2.0 [ Designated as safety issue: Yes ]

Study Start Date: December 2002
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the event-free survival of patients with newly diagnosed anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma (DIPG) treated with adjuvant temozolomide administered concurrently with postoperative radiotherapy and then alone as maintenance therapy vs historical control cohorts treated in prior Pediatric Oncology Group and Children's Cancer Group studies.
  • Determine the toxicity of this regimen in these patients.
  • Determine the efficacy of this regimen in patients with DIPG.
  • Determine the toxicity of this regimen in patients with DIPG.

OUTLINE: This is a multicenter study.

  • Adjuvant chemoradiotherapy: Beginning within 6 weeks after surgical resection or diagnosis*, patients without gross residual disease undergo cranial irradiation 5 days a week for 6 weeks. Beginning within 6 weeks after surgical resection, patients with gross residual disease undergo radiotherapy as above followed by boost radiotherapy for 1 week. All patients receive oral temozolomide once daily beginning within 5 days after initiation of radiotherapy and continuing for a total of 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Adjuvant maintenance therapy: Beginning 4 weeks after completion of adjuvant chemoradiotherapy, patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *For patients with diffuse intrinsic pontine glioma only

Patients are followed every 3-6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 50-60 patients will be accrued for this study within 12-14 months.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed CNS tumor of the following types:

    • High grade glioma (HGG) of one of the following histologies:

      • Anaplastic astrocytoma (grade III)
      • Glioblastoma multiforme (grade IV)
      • Gliosarcoma
      • Primary spinal cord malignant glioma
    • Diffuse intrinsic pontine glioma (DIPG)

      • Diagnosed by gadolinium-enhanced MRI
      • At least 2/3 of tumor situated in the pons AND tumor clearly originated in the pons
      • No diffuse leptomeningeal disease
      • No tumors with features not typical of diffuse intrinsic brainstem glioma, including any of the following:

        • Dorsally exophytic brainstem glioma
        • Cervico-medullary junction tumor
        • Focal low-grade glioma of the midbrain or brainstem
      • No diffuse brainstem enlargement due to neurofibromatosis
  • No primary brain stem malignant glioma
  • No M+ disease (CSF positive for tumor or metastatic disease)
  • Must begin study radiotherapy within 6 weeks after surgical resection (for HGG patients) or diagnosis (for DIPG patients)

PATIENT CHARACTERISTICS:

Age:

  • 3 to 21

Performance status:

  • Karnofsky 50-100% OR
  • Lansky 50-100%

Life expectancy:

  • At least 2 months

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3*
  • Hemoglobin at least 10.0 g/dL* NOTE: *Transfusion independent

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT less than 2.5 times ULN

Renal:

  • Creatinine no greater than 1.5 times ULN

Other:

  • No other concurrent malignancy
  • Concurrent seizure disorder allowed if well controlled on anticonvulsants
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

Biologic:

  • No concurrent routine cytokine support

Chemotherapy:

  • Not specified

Endocrine therapy:

  • No concurrent corticosteroids except for increased intracranial pressure in patients with CNS tumors

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • See Disease Characteristics

Other:

  • No prior therapy for HGG or DIPG
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00028795

  Show 230 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Kenneth J. Cohen, MD, MBA Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Cohen KJ, Heideman RL, Zhou T, Holmes EJ, Lavey RS, Bouffet E, Pollack IF. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: A report from the Children's Oncology Group. Neuro Oncol. 2011 Feb 22; [Epub ahead of print]
Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, Brat DJ, Rosenblum MK, Hamilton RL, Lavey RS, Heideman RL. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol. 2011 Mar;13(3):317-23.
Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50.
Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; The Children’s Oncology Group. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the children's oncology group. J Neurooncol. 2010 Jul 4; [Epub ahead of print]
Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Nikiforov YE, Lyons-Weiler MA, Laframboise WA, Burger PC, Brat DJ, Rosenblum MK, Gilles FH, Yates AJ, Zhou T, Cohen KJ, Finlay JL, Jakacki RI; for the Children's Oncology Group. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: A report from the children's oncology group. Pediatr Blood Cancer. 2010 Jun 29; [Epub ahead of print]

ClinicalTrials.gov Identifier: NCT00028795     History of Changes
Other Study ID Numbers: CDR0000069135, COG-ACNS0126
Study First Received: January 4, 2002
Last Updated: February 26, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
childhood brain stem glioma
childhood high-grade cerebral astrocytoma
childhood spinal cord neoplasm
untreated childhood brain stem glioma

Additional relevant MeSH terms:
Astrocytoma
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Glioblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012