In the first phase of this study (Cohort 1), the investigators will determine the feasibility of adding MRSI to the evaluation of newly-diagnosed GBM patients treated with standard RT/TMZ and determine whether magnetic resonance spectroscopic imaging (MRSI) can predict for better outcomes in these patients. In the second phase of this study (Cohorts 2a and 2b), the investigators will find the maximum tolerated dose of belinostat for treating newly-diagnosed GBM patients with standard RT/TMZ and will determine whether MRSI can aid clinicians in the early determination of response to this new therapy.

Patients will be assigned to Cohort 1 (standard RT/TMZ) followed by entry to either Cohort 1 or Cohort 2a (standard RT/TMZ + dose finding for belinostat), followed by assignment to Cohort 2b (standard RT/TMZ + tolerable dose of belinostat).

Patients will undergo MRSI scans before beginning treatment and then at several time points during treatment to look for the early response of their tumor to treatment. Blood and tumor samples will be used to measure the levels of certain markers within the cancer cells. Patients will also be assessed for the side effects they experience. Progression-free and overall survival outcomes will be recorded. Patients will also have assessment of their depressive symptoms, quality-of-life and neurocognitive function at several time points during and after therapy course.

Inclusion Criteria:

• Newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically

• ≥ 18 years of age

• Able to have MRI scans

• Measurable contrast-enhancing supratentorial tumor (≥ 0.2 cc (current resolution of MRSI is 0.108cc)) in a region amenable to MRSI

• Have the following lab values ≤ 14 days prior to registration:

  • white blood cell count ≥ 3,000/μL
  • absolute neutrophil count ≥ 1,500/μL
  • platelet count of ≥ 100,000/μL
  • hemoglobin ≥ 10 gm/dL (transfusion is allowed to reach minimum level)
  • serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0x upper normal limit (UNL)
  • bilirubin ≤ 2 x UNL
  • creatinine ≤ 1.5 mg/dL

• Life expectancy of ≥ 12 weeks

• Karnofsky Performance Score ≥ 60

• Women of childbearing potential must have a negative beta-human chorionic gonadotropin pregnancy test documented ≤ 7 days prior to registration

• All men and women of childbearing potential must agree to use adequate barrier contraception for the duration of study participation and for 12 weeks after the last dose of study drug (If pregnancy or suspected pregnancy occur while participating in study, treating physician should be informed immediately)

• Understand and provide written informed consent

• Both men and women, and members of all races and ethnic groups are eligible for this trial (Subjects will be approximately representative of the demographics of the referral base for the participating institutions)

• Able to swallow capsules

• Willing to provide mandatory tissue samples (unstained slides) for research purposes

• Willing to forego other cytotoxic and non-cytotoxic therapies against the tumor while being treated on this protocol

Exclusion Criteria:

• Pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue

• Any 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

• History of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible

• Active infection or serious intercurrent medical illness

• Any disease that will obscure toxicity or dangerously alter drug metabolism

• Receiving any other investigational agents

• Received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor

• History of prior cranial radiation

• History of myocardial infarction or unstable angina ≤ 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmias

• Patients with congenital long QT syndrome (for cohorts 2a and 2b [belinostat cohorts] only, ECG not required for cohort 1)

• Has prolonged corrected QT (QTc) interval (> 450 msec) (for cohorts 2a and 2b [belinostat cohorts] only, ECG not required for cohort 1)

• Taking any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes ≤ 7 days prior to registration (for cohorts 2a and 2b [belinostat cohorts] only)

  • 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

• Taking valproic acid ≤ 2 weeks prior to initiation of belinostat therapy (for cohorts 2a and 2b [belinostat cohorts] only)

• Residual enhancing tumor that lies completely within 1-2 cm of the inner table of the skull (Please consult study neuroradiologist or study PIs at your site if there is uncertainty regarding this exclusion criteria)

• May not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy. (Note: patients on the standard therapy arm of another GBM trial that otherwise meet eligibility requirements for this trial remain eligible for cohort 1)