Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

Inclusion Criteria:

- Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM)
or gliosarcoma (GS)

- Diagnosis will have been established by biopsy or resection within 4 weeks prior to
registration

- Patients must not have received previous radiotherapy to the brain

- Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy,
or experimental drug therapy directed against the brain tumor; patients who received
Gliadel wafers will be excluded; patients may have received or be receiving
corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent
complications

- Cranial MRI or contrast CT must have been performed within 21days of study entry; the
use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must
be used throughout the period of protocol treatment for tumor measurement; if the
surgical procedure was a resection, cranial MRI or contrast CT performed with 96
hours of resection is preferred but not required; patients without measurable or
assessable disease are eligible

- Patients must have a plan to begin partial brain radiotherapy within 5-9 days after
beginning R115777, and within 35 days (5 weeks) of the surgical procedure that
established the diagnosis; radiotherapy must be given at the Radiation Oncology
Department of the registering ABTC institution; radiotherapy must be given by
external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned
total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will
not be allowed

- Patients must be willing to forego other drug therapy against the tumor while being
treated with R115777 and temozolomide

- All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study; patients must sign an authorization for the
release of their protected health information; patients must be registered with the
Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study
drug

- Life expectancy > 8 weeks

- Patients must have a Karnofsky performance status of >= 60

- Patients must have adequate bone marrow function and the test must be performed
within 14 days prior to registration; eligibility level for hemoglobin may be reached
by transfusion

- WBC >= 3,000/µl

- ANC >= 1,500/mm^3

- Platelet count of >= 100,000/mm^3

- Hemoglobin >= 10 gm/dl

- Patients must have adequate liver function and the test must be performed within 14
days prior to registration

- SGOT < 2 times ULN

- Bilirubin < 2 times ULN

- Patients must have adequate renal function before starting therapy and the test must
be performed within 14 days prior to registration

- Creatinine < 1.5 mg/dL

- Patients must not have any significant medical illnesses that in the investigator's
opinion cannot be adequately controlled with appropriate therapy or would compromise
the patient's ability to tolerate this therapy; patients must not have any disease
that will obscure toxicity or dangerously alter drug metabolism

- 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

- This study was designed to include women and minorities, but was not designed to
measure differences of intervention effects; males and females will be recruited with
no preference to gender; no exclusion to this study will be based on race; minorities
will actively be recruited to participate

- Patients must not have active infection

- Women must not be pregnant or Breast-feeding, and women with reproductive potential
must practice adequate contraception; the anti-proliferative effects of the
investigational agent may be detrimental to the developing fetus or nursing infant

- Patients must not be on chronic coumadin therapy for prior medical problems (e.g.
cardiac valve prophylaxis); this is due to a presumed interaction with coumadin and
ZARNESTRA leading to a significant increase in INR; patients who develop or have
recently developed a deep venous thrombosis or pulmonary embolism who are on or will
take coumadin will be allowed to participate; however, the investigator should be
prepared to monitor patients INR closely