| 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. |