Inclusion Criteria

Inclusion:

- Patients with histologically proven supratentorial glioblastoma multiforme (GBM).

- 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.

- 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.

- 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.

- 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.

- Patients having undergone recent resection of recurrent or progressive tumor will be
eligible as long as all of the following conditions apply:

1. They have recovered from the effects of surgery.

2. Residual disease following resection of recurrent tumor is not mandated for
eligibility into the study. To best assess the extent of residual disease
post-operatively, a CT/ MRI should be done no later than 96 hours in the
immediate post-operative period or at least 4 weeks post-operatively, within 14
days prior to registration. If the 96-hour scan is more than 14 days before
registration, the scan needs to be repeated. If the steroid dose is increased
between the date of imaging and registration, a new baseline MRI/CT is required
on a stable steroid dosage for at least 5 days.

- Patients must be > 18 years old, and with life expectancy > 8 weeks.

- Patients must have a Karnofsky performance status of > 60 (Karnofsky Performance
Scale; Appendix C).

- 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.

- Patients must have adequate bone marrow function (ANC> 1,500/mm3 and platelet count
of > 100,000/mm3), adequate liver function (SGPT and alkaline phosphatase <2 times
normal, bilirubin <1.5 mg%), and adequate renal function (BUN and creatinine <1.5
times institutional normal) prior to starting therapy.

- Patients must have a normal QT interval on an EKG done within 2 weeks prior to study
entry.

- Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin
anticonvulsants. Patients changing from these anticonvulsants to others that are
allowed must be off the drugs listed above for at least 72 hours.

- Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
for that disease for a minimum of 3 years are ineligible.

- Patients must not have:

1. active infection

2. disease that will obscure toxicity or dangerously alter drug metabolism

3. serious intercurrent medical illness.

4. prior recurrence with either Temozolomide or a farnesyl transferase inhibitor

5. oral contraceptives and other hormonal methods (Depo-Provera) of birth control.

- Patients must not be pregnant and both male and female patients must practice
adequate contraception.

Exclusion:

- Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
for that disease for a minimum of 3 years are ineligible.

- Patients with the following are ineligible:

1. active infection

2. pregnancy and must practice adequate contraception

3. disease that will obscure toxicity or dangerously alter drug metabolism

4. serious intercurrent medical illness

5. previous treatment with either Temozolomide or a farnesyl transferase inhibitor

6. oral contraceptives and other hormonal methods (Depo-Provera) of birth control.