Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	NCI-07-C-0052 AOI-NCI-07-C-0052, NCT00436436

Objectives

1. 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.
2. Determine, preliminarily, the toxicity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

• 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 agents

Patient Characteristics:

• 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

Expected Enrollment

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

Outcomes

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

Objective tumor response rate in patients with MGMT-negative tumors as assessed by IHC
Toxicity as assessed by CTCAE v 3
Best overall response
Progression-free survival
Overall survival

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 months.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Howard Fine, MD, Principal investigator		Ph: 301-402-6298

Registry Information
Official Title		A Phase 2 Study of O6-Benzylguanine (O6-BG) and Temozolomide in Patients with Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment with Radiation Therapy and Temozolomide
Trial Start Date		2006-12-15
Trial Completion Date		2010-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00436436
Date Submitted to PDQ		2007-01-03
Information Last Verified		2008-10-24