Overview

This trial is active, not recruiting.

Condition brain and central nervous system tumors
Treatments o6-benzylguanine, temozolomide
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date December 2006
End date December 2010
Trial size 100 participants
Trial identifier NCT00436436, AOI-NCI-07-C-0052, CDR0000529875, NCI-07-C-0052

Summary

RATIONALE: Drugs used in chemotherapy, such as O(6)-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. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving O(6)-benzylguanine together with temozolomide works in treating patients with glioblastoma multiforme that did not respond to previous temozolomide and radiation therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Masking open label
Primary purpose treatment

Primary Outcomes

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

Secondary Outcomes

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

Eligibility Criteria

Male or female participants at least 18 years old.

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 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 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

Additional Information

Official title 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
Principal investigator Howard A. Fine, MD
Description 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. 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. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in December 2008.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).