Phase I/Ib Study of Sarasar and Temodar in Patients With Recurrent or Temodar-Refractory Glioblastoma Multiforme

Inclusion Criteria:

1. Patients with histologically proven supratentorial glioblastoma multiforme (GBM) or
gliosarcoma.

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 treating physician to document tumor volume
changes to provide a gross assessment of growth rate.

3. Patients may have had as many as 2 prior chemotherapy regimens for recurrent or
progressive tumor. Patients must have had prior treatment with Temodar but may not
have had prior treatment with farnesyl transferase inhibitors (Sarasar or Zarnestra).
Patients in phase 1b expansion are required to have received a minimum of two cycles
of adjuvant TMZ.

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 or decreasing 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 having had recent resection of recurrent or progressive tumor are eligible as
long as: a) Patients must be status post surgical resection at least 2 weeks prior to
study enrollment, have recovered from surgery, have adequate early wound healing and
a Karnofsky performance status of > or = 60.

7. Continued from Inclusion #6. b) Residual disease following resection of recurrent
tumor is not mandated for eligibility into the study. A CT/ MRI should be done within
96 hrs post-op or at least 4 wks post-op (within 14 days of registration). If the
steroid dose is increased between the scan date and registration, a new baseline
MRI/CT is required on a stable steroid dose for 5 days.

8. Patients must be >/= 18 years of age.

9. Patients must have a Karnofsky performance status of >/= 60.

10. 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.

11. 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
<2.5 times normal, bilirubin <1.5 mg%), and adequate renal function (BUN and
creatinine <1.5 times institutional normal) prior to starting therapy.

Exclusion Criteria:

1. Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin
anticonvulsants. Patients changing from these anticonvulsants to other allowable
drugs that are not enzyme inducing anti-epileptic drugs (EIAEDs) must be off the
drugs listed above for at least 72 hours prior the initiation of treatment.

2. 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.

3. Patients must not have: a) uncontrolled active infection b) disease that will obscure
toxicity or dangerously alter drug metabolism c) serious intercurrent medical
illness. d) prior recurrence with a farnesyl transferase inhibitor e) oral
contraceptives and other hormonal methods (Depo-Provera) of birth control.