The goal of this clinical research study is to find the highest safe dose of the new drug ZARNESTRA (R115777) and temozolomide that can be given to patients with brain tumors (glioblastoma multiforme, GBM). The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors. The safety of this treatment will also be studied.

Temozolomide works by killing cancer cells. R115777 is a new drug that may slow down the growth of cancer cells. Used in combination, the two drugs may control the growth of brain tumors.

Before treatment starts, patients will have a complete exam, including measurement of height and weight. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan will be done. Women who are able have children must have a negative blood pregnancy test.

Temozolomide and R115777 will both be taken by mouth. Participants in this study will take temozolomide once a day for 7 days every other week (Days 1-7 and 15-21). This will be repeated every 28 days (1 course). Patients must not eat for 1 hour before and after taking the drug; drinking water is allowed. All treatment may be given on an outpatient basis.

During the alternate weeks (Days 8-14 and 22-28), participants will take R115777 tablets by mouth in the morning and evening with food. At the beginning of the study, groups of 3 participants each will take increasing doses of both R115777 and temozolomide until the highest safe dose of each drug, when given in combination, is found. Participants entering the study after the highest safe dose is found will receive that dosage.

If tumors do not grow and serious side effects do not occur, participants may keep on taking temozolomide and R115777 for up to 2 year. If your physician thinks it is advisable, treatment may continue with R115777 alone after that time. In this case, routine blood tests for counts, liver and kidney function (less than 2 tablespoons) will be repeated every 4 weeks and MRI scans, physical, and neurological exams will be done every 8 weeks. Participants may not receive any other treatment for cancer (including surgery) while taking part in this study.

Participants will come to the clinic to have a complete physical and neurological exam and blood tests (less than 2 tablespoons of blood) before each course. Blood tests will be repeated once a week for the first 2 courses of treatment and then on Days 14 and 28 of each later course. A MRI scan will be done before the odd-numbered (3, 5, 7, etc.) courses of treatment or at any time clinically indicated.

At the end of the study, participants will have another complete physical exam. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan will be done.

This is an investigational study. Temozolomide is approved by the FDA for the treatment of some brain tumors and is commercially available. R115777 is approved for research use only in the treatment of brain tumors. The use of these two drugs together is experimental.

Inclusion Criteria:

1. Patients with histologically proven supratentorial glioblastoma multiforme (GBM).
2. Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan after radiation therapy. The scan done prior to study entry documenting progression will be reviewed by the primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
3. Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
4. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.
5. Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
6. Pts with recent resection of recurrent or progressive tumor will be eligible if all of the following conditions apply: Pt has recovered from the effects of surgery; Residual disease after resection of recurrent tumor is not mandated for eligibility. To assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours post-operatively or at least 4 weeks post-operatively, and within 14 days before registration. If steroid dose increased between the day of imaging and registration, a new baseline scan is required after stable steroids for 5 days.
7. Patients must have a Karnofsky performance status of >/= 60
8. Patients must have recovered from the toxic effects of prior therapy: 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
9. Patients must have adequate bone marrow function (ANC>/= 1,500/mm(3) and platelet count of >/= 100,000/mm(3)), adequate liver function (SGPT and SGOT \

2 years, 11 months

Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.