Chemotherapy and Radiation Therapy After Surgery in Treating Children With Newly Diagnosed Astrocytoma, Glioblastoma Multiforme, Gliosarcoma, or Diffuse Intrinsic Pontine Glioma

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ClinicalTrials.gov Identifier: NCT00028795

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : February 21, 2014

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	170 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Study of Temozolomide in the Treatment of Children With High Grade Glioma
Study Start Date :	December 2002
Actual Primary Completion Date :	September 2007
Actual Study Completion Date :	March 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Diffuse Intrinsic Pontine Glioma Gliosarcoma Childhood Brain Stem Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Chemoradiotherapy	Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures :

Improved outcome
Toxicity as assessed by NCI CTCAE v. 2.0

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	3 Years to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
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

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): NCT00028795

Show 230 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

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Study Chair:	Kenneth J. Cohen, MD, MBA	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

More Information

Publications of Results:

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 Apr;13(4):410-6. doi: 10.1093/neuonc/noq205. Epub 2011 Feb 22.

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. doi: 10.1093/neuonc/noq191.

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.

Other Publications:

Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; 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 Sep;99(2):155-63. doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.

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; 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 Dec 1;55(6):1066-71. doi: 10.1002/pbc.22634.

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Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00028795 History of Changes
Other Study ID Numbers:	ACNS0126 COG-ACNS0126 ( Other Identifier: Children's Oncology Group ) CDR0000069135 ( Other Identifier: Clinical Trials.gov )
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	February 21, 2014
Last Verified:	February 2014

Keywords provided by Children's Oncology Group:


childhood brain stem glioma childhood high-grade cerebral astrocytoma childhood spinal cord neoplasm untreated childhood brain stem glioma

Additional relevant MeSH terms:

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Glioma Astrocytoma Nervous System Neoplasms Central Nervous System Neoplasms 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 Antineoplastic Agents

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