This clinical trial is studying magnetic resonance spectroscopy imaging in predicting response in patients to vorinostat and temozolomide in patients with recurrent, progressive, or newly diagnosed glioblastoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help temozolomide work better by making tumor cells more sensitive to the drug. Imaging procedures, such as magnetic resonance spectroscopy imaging, may help measure the patient's response to vorinostat and temozolomide and allow doctors to plan better treatment.

PRIMARY OBJECTIVES:

I. To evaluate the strength of the association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide.

SECONDARY OBJECTIVES:

I. To evaluate MRS-detected inositol and N-acetylaspartate (NAA) levels (at 3 tesla) as indicators of mood alterations as measured by a self-report depression survey (IDS-SR).

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) on days -7 to -1 (course 1 only) and days 8-14 and 22-28 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients previously treated with standard radiotherapy and temozolomide receive maintenance temozolomide PO on days 1-5.

Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities. Patients undergo magnetic resonance spectroscopy imaging at baseline and at approximately 1 and 8 weeks on treatment. Patients also undergo an Inventory of Depression Symptomatology Self-Reported (IDS-SR) assessment at baseline and periodically during study.

Inclusion Criteria:

• Patients must have 1 of the following:

  • Diagnosis of recurrent or progressive glioblastoma

    • Patients with recurrent disease may have had treatment for any number of prior relapses

  • Newly diagnosed glioblastoma and have completed radiation therapy and are receiving standard follow-up temozolomide

• Must be able to have an MRI, and have a measurable contrast-enhancing supratentorial tumor of at least 1 cm by shortest diameter

• Residual disease following resection measuring 1 cm in diameter or greater is mandated for eligibility into the study

• Patients must have a stable or progressive disease as determined by serial brain MRI using the McDonald Criteria on a scan 14 days or fewer before registration and on a stable steroid dose for 5 days

• 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 positron emission tomography (PET) or thallium scanning, MR spectroscopy, or surgical documentation of disease

• White Blood Cell Count > 3,000/μL

• Absolute Neutrophil Count > 1,500/μL

• Platelet count > 100,000/μL

• Hemoglobin > 10 g/dL (transfusion allowed)

• Serum glutamate oxaloacetate transaminase < 2 times upper limit of normal (ULN)

• Bilirubin < 2 times ULN

• Creatinine < 1.5 mg/dL

• Negative pregnancy test

• Women of childbearing potential and men must agree to use adequate barrier contraception for the duration of study participation

• Able to swallow capsules

• No patients with pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, history of being a steel worker, or other incompatible implants

• No significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

• No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix, or cancer in complete remission and off all therapy for ≥ 3 years

• No active infection or serious intercurrent medical illness

• No disease that would obscure toxicity or dangerously alter drug metabolism

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in this study

• No prolonged corrected QT interval waves on baseline EKG

• No other anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy) of any kind is permitted during the study period

• At least 3 weeks since prior radiotherapy

• Patients must have recovered from the toxic effects of prior therapy, including surgery

• At least 28 days since any prior investigational agent or prior cytotoxic therapy

• At least 23 days since prior temozolomide

• At least 14 days since prior vincristine (42 days for nitrosourea)

• At least 21 days since prior procarbazine

• At least 7 days since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.)

• At least 2 weeks since prior valproic acid (or another histone deacetylase inhibitor)

• No other concurrent investigational agents

Exclusion Criteria:

• Diagnostic and Statistical Manual-IV Axis I or II diagnosis (as determined by PI), exclusive of nicotine dependence.
• Pregnant.
• Contraindications to MRI: pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants.
• Active medical or neurological disorder.
• History of alcohol or drug dependence