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A Phase 2 Study of O-Benzylguanine (O-BG) and Temozolomide in Patients With Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment With Radiation Therapy and Temozolomide

Phase 2
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors

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Trial Information

A Phase 2 Study of O-Benzylguanine (O-BG) and Temozolomide in Patients With Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment With Radiation Therapy and Temozolomide


- Determine the antitumor activity of O6-benzylguanine and temozolomide in patients with
temozolomide-resistant methylguanine methyltransferase-positive or -negative
glioblastoma multiforme previously treated with radiotherapy.

- Determine, preliminarily, the toxicity of this regimen in these patients.

OUTLINE: Patients receive O6-benzylguanine IV over 1 hour and oral temozolomide once daily
on days 1-5. Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 6

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed glioblastoma multiforme (GBM), including the following:

- Small or large cell GBM

- Gliosarcoma

- Temozolomide-resistant disease, as defined by the following:

- Unequivocal evidence of tumor progression after receiving adjuvant temozolomide
therapy for 5 consecutive days every 28 days for ≥ 2 courses

- Must have failed prior radiotherapy

- Progression must be documented by MRI (while on a stable steroid dose for ≥ 5
days) ≥ 12 weeks after completion of radiotherapy

- Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded
microscope slides available from diagnosis


- Karnofsky performance status 60-100%

- Life expectancy > 8 weeks

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 10 g/dL (transfusion allowed)

- AST < 2 times upper limit of normal (ULN)

- Bilirubin < 2 times ULN

- Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min

- No significant medical illness that, in the opinion of the investigator, would
preclude study compliance

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No significant active cardiac, hepatic, renal, or psychiatric disease

- No other known active malignancy except for nonmelanoma skin cancer or carcinoma in
situ of the cervix

- No active infection requiring IV antibiotics

- No disease that would obscure toxicity or alter drug metabolism


- See Disease Characteristics

- Recovered from prior temozolomide

- Prior resection of recurrent or progressive tumor allowed if all the following
criteria are met:

- Recovered from prior surgery

- Residual disease after resection of recurrent tumor by CT scan or MRI (while on
a stable steroid dose for ≥ 5 days) ≤ 96 hours OR ≥ 4 weeks after surgery

- At least 12 weeks since prior radiotherapy

- No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel
wafers] or nitrosoureas)

- No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed best objective tumor response rate (complete or partial response) in patients with methylguanine methyltransferase (MGMT)-positive tumors as assessed by immunohistochemistry (IHC)

Safety Issue:


Principal Investigator

Howard A. Fine, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Neuro-Oncology Branch


United States: Food and Drug Administration

Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • recurrent adult brain tumor
  • adult glioblastoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182
NCI - Neuro-Oncology Branch Bethesda, Maryland  20892-8200