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

• Status: Terminated
• Trial end date: 2010-04-14
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Dacarbazine; O(6)-benzylguanine; Temozolomide

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

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Life expectancy > 8 weeks

• White blood cell (WBC) ≥ 3,000/mm(³)

• Absolute neutrophil count ≥ 1,500/mm(³)

• Platelet count ≥ 100,000/mm(³)

• Hemoglobin ≥ 10 g/dL (transfusion allowed)

• Aspartate aminotransaminase (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 intravenous (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 computed tomography (CT) scan or magnetic resonance imaging (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