Suberoylanilide Hydroxamic Acid (SAHA), Bevacizumab, Daily Temozolomide for Recurrent Malignant Gliomas

Inclusion Criteria:

* Patients must have histologically confirmed diagnosis of malignant glioma and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement or a new enhancing lesion) following prior therapy. In addition, the following must be met:

Phase I specific

* WHO grade 3 or 4 malignant glioma Phase II specific
* WHO grade 4 malignant glioma
* No more than 2 prior episodes of disease progression

Common to both Phase I and Phase II

* Age \* 18 years
* KPS (Karnofsky Performance Scale) ≥ 70%
* An interval of at least 4 weeks between prior surgical resection or one week from stereotactic biopsy
* An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there are progressive changes on MRI on at least two consecutive MRI scans at least four weeks apart, or there is biopsy-proven tumor progression
* An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or investigational agent unless the patient has recovered from all anticipated toxicities associated with that therapy
* Hematocrit ≥ 29%, ANC ≥ 1,000 cells/\*l, platelets ≥ 100,000 cells/\*l
* Serum creatinine \< 1.5 times upper limit of normal, serum SGOT \< 2.5 times upper limit of normal and bilirubin \< 2.0 times upper limit of normal
* Signed informed consent approved by the Institutional Review Board prior to patient entry
* No evidence of hemorrhage on the baseline MRI or CT scan other than those that are stable grade 1
* If sexually active, patients will take contraceptive measures for the duration of the treatments. Medically acceptable contraceptives include:

  1. surgical sterilization (such as a tubal ligation, hysterectomy, vasectomy),
  2. approved hormonal contraceptives (such as birth control pills, patches, implants or injections),
  3. barrier methods (such as a condom or diaphragm) used with a spermicide, or
  4. an intrauterine device (IUD).

Exclusion Criteria:

* Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and patients previously treated with valproic acid must be off valproic acid for at least 30 days prior to initiation of study medication
* Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
* Active infection requiring intravenous antibiotics
* Progression on prior bevacizumab or daily temozolomide
* Grade 3 or greater toxicity related to prior bevacizumab or daily temozolomide therapy
* Requires therapeutic anti-coagulation with warfarin
* Life expectancy of \<12 weeks
* Active malignancy other than basal or squamous cell skin ca or carcinoma in situ of cervix within 5 years
* Subject recruitment and compensation - subjects will be recruited for this study as follows:

  * Upon determination that a subject's tumor histology and/or radiographic findings are compatible with the eligibility criteria of this protocol, the clinical study will be briefly explained to the subject by the subject's physician, who will be a physician at the Brain Tumor Center at Duke.
  * If the subject indicates interest in study participation, subject education sheets and the informed consent document will be provided to the subject as these provide the most comprehensive explanation of the study in lay terms.
  * If the subject shows continued interest, the PI or designee will thoroughly explain the required elements of the consent form and all aspects of the study to the subject including inclusion/exclusion criteria, risks, benefits, and alternatives to study participation.
  * Subjects will not be paid to take part in this research study.

The list of subjects pre-screened will be kept in an Excel spreadsheet in the study coordinator's office. The PC (personal computer) is on the DUHS (Duke University Health System) network protected by a user ID (identifier) and password and the office is locked when it is unoccupied. All screened subjects who are not enrolled in the study will have all identifiers destroyed immediately.