O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy
This trial is active, not recruiting.
|Condition||brain and central nervous system tumors|
|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|
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|
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
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
|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.|
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