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O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors
This study is ongoing, but not recruiting participants.
First Received: January 10, 2006   Last Updated: August 27, 2009   History of Changes
Sponsors and Collaborators: Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00275002
  Purpose

RATIONALE: Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: O6-benzylguanine
Drug: temozolomide
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response at 8 weeks [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2006
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the sustained objective response rate to the combination of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas or brain stem tumors.

Secondary

  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (high-grade gliomas vs brain stem tumors).

Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed* high-grade glioma or brain stem tumor, including any of the following:

    • Anaplastic astrocytoma
    • Glioblastoma multiforme
    • Anaplastic oligodendroglioma
    • Anaplastic ganglioma
    • Gliosarcoma NOTE: *Histologic confirmation not required for brain stem tumors
  • Recurrent or progressive disease after treatment with standard therapy

    • Radiotherapy allowed if considered standard treatment for primary or salvage therapy in advanced of a phase II regimen for the respective disease and presentation
    • No more than 2 recurrences or progressions
  • Bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions

    • Diffuse meningeal involvement is not considered measurable disease

PATIENT CHARACTERISTICS:

Performance status

  • Karnofsky 60-100% (for patients > 16 years of age) OR
  • Lansky 60-100% (for patients ≤ 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3 (unsupported)
  • Hemoglobin > 8 g/dL (may be supported)
  • Absolute lymphocyte count ≥ 500/mm^3

Hepatic

  • SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • No overt hepatic disease

Renal

  • Creatinine clearance ≥ 60 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
    • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
    • No greater than 1.5 mg/dL (for patients > 15 years of age)
  • No overt renal disease

Cardiovascular

  • No overt cardiac disease

Pulmonary

  • No overt pulmonary disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of severe toxicity (≥ grade 3) associated with temozolomide
  • No history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
  • No infection
  • No uncontrolled significant systemic illness
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 3 weeks since prior biologic therapy
  • At least 6 months since prior allogeneic bone marrow transplantation
  • At least 3 months since prior autologous bone marrow or stem cell transplantation
  • At least 2 weeks since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)

Chemotherapy

  • At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)
  • Prior temozolomide allowed

Endocrine therapy

  • Concurrent corticosteroid therapy allowed

Radiotherapy

  • See Disease Characteristics
  • At least 3 months since prior craniospinal irradiation
  • At least 3 months since prior primary tumor local irradiation

Other

  • Recovered from all prior therapy
  • At least 1 week since prior nonmyelosuppressive investigational agents or anticancer drugs
  • No other concurrent anticancer or investigational therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00275002

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Study Chair: Katherine Warren, MD NCI - Pediatric Oncology Branch
Investigator: Sri Gururangan, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital ( James M. Boyett )
Study ID Numbers: CDR0000455561, PBTC-015, NCI-06-C-0089, NCI-P6692
Study First Received: January 10, 2006
Last Updated: August 27, 2009
ClinicalTrials.gov Identifier: NCT00275002     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent childhood brain stem glioma
recurrent childhood brain tumor

Study placed in the following topic categories:
Brain Stem Neoplasms
Central Nervous System Diseases
Brain Tumor, Childhood
Central Nervous System Neoplasms
Brain Diseases
Temozolomide
Recurrence
Brain Neoplasms
Brain Stem Glioma, Childhood
O(6)-benzylguanine
Glioma
Antineoplastic Agents, Alkylating
Alkylating Agents
Nervous System Neoplasms

Additional relevant MeSH terms:
Disease Attributes
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Brain Stem Neoplasms
Central Nervous System Diseases
Enzyme Inhibitors
Central Nervous System Neoplasms
Brain Diseases
Temozolomide
Pharmacologic Actions
Recurrence
Brain Neoplasms
Neoplasms
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Infratentorial Neoplasms
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Alkylating Agents
Nervous System Neoplasms

ClinicalTrials.gov processed this record on September 02, 2009