|Inclusion Criteria:||1) Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made.|
2) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered with the Adult Brain Tumor Consortium(ABTC) Central Office database prior to treatment with study drug.
3) Patients must be >/= 18 years old, and with a life expectancy > 8 weeks.
4) Patients must have a Karnofsky performance status of >/= 60.
5) Patients must have adequate bone marrow function (WBC >/= 3,000/Ál, ANC >/= 1,500/mm^3, platelet count of >/= 100,000/mm^3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
6) A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable 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.
7) Patients must have an interval of greater than or equal to 3 weeks (21) days from the completion of radiation therapy to study entry.
8) Women of childbearing potential must have a negative beta-HCG pregnancy test documented within 7 days prior to registration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
9) The effects of vorinostat (SAHA) on the developing human fetus are unknown. For this reason, and because HDAC inhibitors (as well as temozolomide) are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of participation in the study.
10) Patients in Part 1 only: Patients with either stable disease after radiation therapy or with progression are eligible (except if they have progressed on temozolomide). Patients who have received prior treatment with temozolomide and have stable disease are eligible.
11) Patients in Part 1 only: Patients with recurrent disease may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy).
12) Patients must have recovered from the toxic effects of prior therapy: 28 days from any investigational agent, 28 days from prior cytotoxic therapy except 23 days from last dose of temozolomide for patients taking the standard 5 days every 28 day regimen of temozolomide,14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration,and 7 days 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.
13) Patients in Part 1 only: Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: (a) They have recovered from the effects of surgery; (b) Residual disease following resection is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration.
14) (continued from 13:Patient in Part 1 only): If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
15) Patients in Part 1 only: Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical documentation of disease.
16) Patients in Part 2 only: Only patients with stable disease after radiation therapy are eligible for Part 2 of the study. Patients with recurrent disease are ineligible.
17) Patients in Part 2 only:The only prior therapy permitted for patients in Part 2 of the study is concomitant temozolomide with radiation therapy or radiation therapy alone. Patients that are stable on adjuvant temozolomide may also participate.
18) Patients must be willing to participate in the pharmacokinetic studies.