Inclusion Criteria:

- Histologically confirmed glioblastoma multiforme

- Gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma)
allowed

- Recurrent disease

- Must have evidence of tumor progression by MRI or CT scan after radiotherapy or after
the most recent antitumor therapy

- Bidimensionally measurable or evaluable disease by MRI or CT scan

- Patients receiving corticosteroids must be on a fixed dose for at least 1 week
prior to baseline scan

- ECOG performance status 0-2

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 3 times ULN

- Creatinine normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after the
last dose of vorinostat

- Willing to provide mandatory correlative laboratory tissue samples

- Able to take oral medications

- No uncontrolled infection

- No known hypersensitivity to any of the components of vorinostat or bortezomib

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

- No congestive heart failure requiring use of ongoing maintenance therapy or history
of life-threatening ventricular arrhythmias

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Psychiatric illness or social situation that would limit compliance with study
requirements

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

- No comorbid systemic illness or other severe concurrent disease that, in the judgment
of the investigator, would preclude study entry or significantly interfere with
proper assessment of safety and toxicity of the prescribed study regimens

- Not immunocompromised

- Patients known to be HIV positive are eligible provided there is no clinical
evidence of an immunocompromised state

- No peripheral neuropathy ≥ grade 2

- No peripheral neuropathy with pain ≥ grade 1

- No congenital long QT syndrome

- No prolonged OTC interval (> 450 msec)

- No other concurrent anticancer therapy (other than hormonal therapy)

- At least 8 weeks since prior radiotherapy

- More than 6 weeks since prior stereotactic radiosurgery or interstitial
brachytherapy, unless there is a separate lesion on MRI that is not part of the prior
treatment field

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- No more than 1 prior chemotherapy regimen* for progressive/recurrent disease (stratum
1)

- Patients in stratum 2 may have received any number of prior chemotherapy
regimens* for progressive/recurrent disease

- More than 2 weeks since prior small molecule cell cycle inhibitors

- More than 7 days since prior valproic acid

- More than 7 days since prior category I drugs that are generally accepted to have a
risk of causing Torsades de Pointes including:

- 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,lidoflazine

- More than 4 weeks since prior bevacizumab

- No prior treatment with vorinostat or bortezomib

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin,fosphenytoin,
carbamazepine, phenobarbital, or primidone)

- No other concurrent potent CYP3A4 inducer (e.g., rifampin or St. John's wort)

- No other concurrent investigational therapy for the primary neoplasm