O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: O6-benzylguanine; temozolomide
Intervention MeSH terms: Temozolomide; O(6)-benzylguanine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult glioblastoma

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.
    

Eligibility 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