Phase I/II Evaluation Temozolomide and Farnesyl Transferase Inhibitor ZARNESTRA (R115777) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme

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 normal, bilirubin times institutional normal) prior to starting therapy.

10. ZARNESTRA may interfere with coumadin dosing and patients who are taking this
combination will require more frequent monitoring of their PT, PTT and INR.

11. Patient has no risk factors for HIV or is serologically negative.

Exclusion Criteria:

1. 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 1 week.

2. Patients must not be taking cimetidine, erythromycin azole antifungals, paclitaxel,
tacrolimus or cyclosporine.

3. Patients must not have uncontrolled high blood pressure, unstable angina, symptomatic
congestive heart failure, myocardial infarction within the previous six months, or
serious uncontrolled cardiac arrhythmia.

4. Because of the concerns of potentially harmful interactions of ZARNESTRA and other
medications taken by patients who are HIV positive or have AIDS related diseases,
patients who are HIV positive will not be eligible for entry into this study. Only
patients with suspected HIV will be tested and if positive, will be ineligible.

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

6. Patients must not have: a) active infection b) disease that will obscure toxicity or
dangerously alter drug metabolism c) serious intercurrent medical illness. d) prior
recurrence with either Temozolomide or a farnesyl transferase inhibitor.

7. Patients must not be pregnant and must practice adequate contraception