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Phase II Study of O6-Benzylguanine and Temozolomide in Patients With Temozolomide-Resistant Glioblastoma Multiforme That Was Previously Treated With Radiotherapy
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 | Protocol IDs |
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Phase II | Treatment | Closed | 18 and over | NCI-07-C-0052 AOI-NCI-07-C-0052, NCT00436436 |
Objectives - 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.
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 100A total of 100 patients will be accrued for this study. Outcomes Primary Outcome(s)Confirmed best objective tumor response rate (complete or partial response) in patients with methylguanine methyltransferase (MGMT)-positive tumors as assessed by immunohistochemistry (IHC)
Secondary Outcome(s)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 | | | |
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 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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