Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas

Inclusion Criteria:

• Patients with histologically proven intracranial malignant glioma will be eligiblefor 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 otherwisespecified); patients will be eligible if the original histology was low-grade gliomaand a subsequent histological diagnosis of a malignant glioma is made

• All patients must sign an informed consent indicating that they are aware of theinvestigational nature of this study; patients must have signed an authorization forthe release of their protected health information; patients must be registered withthe Adult Brain Tumor Consortium (ABTC) Central Office database prior to treatmentwith study drug

• Life expectancy > 8 weeks

• Karnofsky performance status of >= 60

• White blood cell (WBC) >= 3,000/mm^3

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 10 g/dL; eligibility level for hemoglobin may be reached bytransfusion

• Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN)

• Bilirubin < 2 times ULN

• If liver function tests are above the institutional upper limit of normal but < 2times institutional upper limit of normal, the decision to initiate temozolomidetreatment should carefully consider the benefits and risks for the individualpatient

• Creatinine < 1.5 mg/dL

• A scan should be performed within 14 days prior to registration and on a steroiddose that has been stable for at least 5 days; if the steroid dose is increasedbetween the date of imaging and registration a new baseline magnetic resonance (MR)/computed tomography (CT) is required; the same type of scan, i.e., magneticresonance imaging (MRI) or CT must be used throughout the period of protocoltreatment for tumor measurement

• Patients must have an interval of greater than or equal to 3 weeks (21) days fromthe completion of radiation therapy to study entry

• Women of childbearing potential must have a negative beta-human chorionicgonadotropin (HCG) pregnancy test documented within 7 days prior to registration;should a woman become pregnant or suspect she is pregnant while participating inthis study, she should inform her treating physician immediately

• 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 andfor the duration of participation in the study

• Patients must be willing to participate in the pharmacokinetic studies

• ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART I OF THE STUDY

• Patients with either stable disease after radiation therapy or with progression areeligible (except if they have progressed on temozolomide; patients who have receivedprior treatment with temozolomide and have stable disease are eligible

• Patients with recurrent disease may have had treatment for any number of priorrelapses; relapse is defined as progression following initial therapy (i.e.radiation +/- chemo if that was used as initial therapy)

• Patients must have recovered from the toxic effects of prior therapy: 28 days fromany investigational agent, 28 days from prior cytotoxic therapy except 23 days fromlast dose of temozolomide for patients taking the standard 5 days every 28 dayregimen of temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21days from procarbazine administration, and 7 days for non-cytotoxic agents, e.g.,interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer doesnot count); any questions related to the definition of non-cytotoxic agents shouldbe directed to the study chair

• Patients having undergone recent resection of recurrent or progressive tumor will beeligible as long as all of the following conditions apply:

• They have recovered from the effects of surgery

• Residual disease following resection is not mandated for eligibility into thestudy; to best assess the extent of residual disease post-operatively, a CT/MRIshould be done no later than 96 hours in the immediate post-operative period orat least 4 weeks post-operatively, within 14 days prior to registration; if the 96-hour scan is more than 14 days before registration, the scan needs to berepeated; if the steroid dose is increased between the date of imaging andregistration, a new baseline MRI/CT is required on a stable steroid dosage forat least 5 days

• Patients with prior therapy that included interstitial brachytherapy or stereotacticradiosurgery must have confirmation of true progressive disease rather thanradiation necrosis based upon either positron emission tomography (PET) or thalliumscanning, MR spectroscopy or surgical documentation of disease

• ELIGIBILITY CRITERIA SPECIFIC FOR PATIENTS IN PART II OF THE STUDY

• Only patients with stable disease after radiation therapy are eligible for part 2 ofthe study; patients with recurrent disease are ineligible

• The only prior therapy permitted for patients in part 2 of the study is concomitanttemozolomide with radiation therapy or radiation therapy alone; patients that arestable on adjuvant temozolomide may also participate

• Patients with recurrent disease and prior chemotherapies (except concurrent oradjuvant temozolomide) will not be included in this part of the study

Exclusion Criteria:

• Patients who have progressed on temozolomide are ineligible

• Patients must not have any significant medical illnesses that in the investigator'sopinion cannot be adequately controlled with appropriate therapy or would compromisethe patient's ability to tolerate this therapy; patients with a history of any othercancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unlessin complete remission and off of all therapy for that disease for a minimum of 3years are ineligible

• Patients must not have active infection or serious intercurrent medical illness

• Pregnant women are excluded from this study; breastfeeding should be discontinued ifthe mother is treated with vorinostat (SAHA); potential risks may also apply totemozolomide

• Patients must not have any disease that will obscure toxicity or dangerously alterdrug metabolism

• Patients who are known to be human immunodeficiency virus (HIV) positive and arereceiving combination antiretroviral therapy are ineligible

• Patients may not be receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to vorinostat (SAHA) or other agents used in study

• Patients should not have taken valproic acid (another histone deacetylase inhibitor)for at least 2 weeks prior to enrollment