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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

Phase 2
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

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


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


I. 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 to the earliest of 30 days
following discontinuation of therapy or the initiation of additional anti-cancer therapy or

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

Inclusion Criteria


- Tumor: Participants must have a high-grade glioma (including e.g. histologically
confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic
oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor
(histologic confirmation waived) with documentation of disease recurrence or
progression after treatment with standard therapy. Participants must have
bi-dimensionally measurable disease, defined as at least 1 lesion that can be
measured in ≥ 2 dimensions

- Age: 21 years of age or less

- 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: Must have adequate bone marrow function defined as absolute neutrophil
count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL
(may be supported), and absolute lymphocyte count ≥ 500/mm^3

- Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤
1.5 times ULN, and no overt hepatic disease

- Renal: Participants must have 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), or no greater than 1.5 mg/dL (for patients > 15
years of age). There must be no overt renal disease

- Cardiovascular: Must have no overt cardiac disease

- Pulmonary: Must have no overt pulmonary disease

- Other: Female participants of childbearing potential must have a negative pregnancy
test prior to study registration, and must avoid breast-feeding. Female and male
participants of childbearing or child-fathering potential must use effective

- Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow
transplantation and at least 3 months since prior autologous bone marrow or stem cell

- Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors
(e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)

- Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer
chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas.
Must have received last dose of nonmyelosuppressive investigational agents or
anticancer drugs ≥ 7 days prior to study registration. Participants who have received
prior temozolomide are eligible

- Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed

- Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and
local irradiation to the primary tumor ≥ 12 weeks prior to study registration

- Prior Therapy-Other: Must have recovered from all prior therapy


- Must not have history of severe toxicity (≥ grade 3) associated with temozolomide

- Must not be receiving other concurrent anticancer or investigational therapy

- Must not have history of hypersensitivity to dacarbazine, temozolomide, or
polyethylene glycol (PEG)

- Must not have uncontrolled significant systemic illness including infection, or overt
renal, hepatic, cardiac, or pulmonary disease

- Must not be HIV positive

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of Participants With an Objective Response (Complete Response or Partial Response)

Outcome Description:

The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.

Outcome Time Frame:

Week 8, 16, 24, 32, and 40 after starting therapy

Safety Issue:


Principal Investigator

Katherine Warren, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

February 2006

Completion Date:

October 2011

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent childhood brain stem glioma
  • recurrent childhood brain tumor
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Brain Stem Neoplasms



Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Texas Children's Cancer Center and Hematology Service at Texas Children's HospitalHouston, Texas  77030-2399
Dan L. Duncan Cancer Center at Baylor College of MedicineHouston, Texas  77030