Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]), Temozolomide, and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

- Histologically confirmed glioblastoma multiforme, including gliosarcoma or other
grade 4 astrocytoma variant (e.g., giant cell glioblastoma)

- Bidimensionally measurable or evaluable disease by gadolinium MRI or
contrast-enhanced CT scan

- Has undergone surgery for the brain tumor within the past 2-5 weeks

- Karnofsky performance status (PS) 60-100% or ECOG PS 0-2

- Life expectancy ≥ 12 weeks

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

- Total bilirubin ≤ 2.0 times upper normal limit (ULN)

- AST ≤ 2.0 times ULN

- Creatinine ≤ 1.5 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 weeks after
completion of study treatment

- No known hypersensitivity to any of the components of vorinostat or other drugs used
in the study

- No other active malignancy within the past 3 years, except nonmelanotic skin cancer
or carcinoma in situ of the cervix

- No uncontrolled infection

- Known HIV positivity allowed provided there is no clinical evidence of an
immunocompromised state

- No co-morbid systemic illness or other concurrent severe illness that, in the opinion
of the investigator, would preclude study participation

- No concurrent uncontrolled illness (e.g., ongoing or active infection or psychiatric
illness/social situation) that would preclude study compliance

- No myocardial infarction or unstable angina within the past 6 months

- No congestive heart failure requiring ongoing maintenance therapy

- No life-threatening ventricular arrhythmias

- No congenital long QT syndrome

- No prolonged QTc interval (i.e., QTc > 450 msec)

- Able to take oral medications

- Willing to provide mandatory tissue samples for research studies (for patients
treated at the maximum tolerated dose)

- Willing and able to complete neurocognitive assessments (patients enrolled in phase
II and those who are treated at the maximum tolerated dose in phase I)

- No concurrent treatment for another malignancy other than hormonal therapy

- No prior cytotoxic, non-cytotoxic, or experimental drug therapy for the brain tumor

- No prior cranial radiotherapy

- No prior Gliadel wafers

- More than 7 days since prior and no concurrent Category I drugs that have a risk of
causing torsades de pointes (e.g., quinidine, procainamide, disopyramide, amiodarone,
sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine,
haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol,
methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,
pentamidine, sparfloxacin, or lidoflazine)

- More than 2 weeks since prior and no concurrent valproic acid or other histone
deacetylase inhibitors

- Concurrent corticosteroids allowed provided patient is on a fixed or decreasing dose
for ≥ 5 days prior to study enrollment

- No other concurrent investigational agents for the brain tumor

- No other concurrent cytotoxic or non-cytotoxic drug therapy for the brain tumor

- No concurrent stereotactic radiosurgery or brachytherapy

- No concurrent antiretroviral therapy for HIV-positive patients