This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of dimethyl fumarate (DMF) when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed glioblastoma multiforme (GBM).

SECONDARY OBJECTIVES:

I. To evaluate the safety, tolerance, and toxicity of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

II. To obtain a preliminary estimate of the efficacy of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

OUTLINE: This is a dose-escalation study of dimethyl fumarate.

CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide orally (PO) once daily (QD) for 42-49 days and dimethyl fumarate PO twice daily (BID) or thrice daily (TID) continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions.

MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 2 months thereafter.

Inclusion Criteria:

• Histopathologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) following either a surgical resection or biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Subjects must have recovered from surgery or biopsy before study registration
• Therapy must begin between 21 days (3 weeks) and 42 days (6 weeks) after the most recent brain tumor surgery(resection or biopsy)
• Documentation of steroid doses 10-14 days prior to study registration and stable or decreasing steroid dose over the week prior to registration
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 100,000/mm^3 (untransfused)
• Hemoglobin >= 10 g/dL (the use of transfusion or other intervention to achieve hemoglobin >= 10 g/dL is acceptable)
• Creatinine =< 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance > 45 mL/min
• Total bilirubin =< 1.5 x ULN for the laboratory (total bilirubin criteria may be waived if a subject has documented Gilbert's syndrome)
• Aspartate aminotransferase (AST) =< 3 x ULN for the laboratory
• Alanine aminotransferase (ALT) =< 3 x ULN for the laboratory
• Women of childbearing potential and male subjects must practice adequate contraception
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior invasive malignancy (except for non-melanoma skin cancer) unless disease free for >= 3 years
• Recurrent malignant gliomas
• Metastases detected below the tentorium or beyond the cranial vault
• Prior chemotherapy or radiation therapy (RT) for the diagnosis of GBM or for cancers of the head and neck
• Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy
• Pregnant or lactating women
• History of allergic reactions or intolerance to any of the required agents on the study
• History of hypersensitivity to dacarbazine
• Any treatment for GBM, other than surgery or anti-epileptic therapy, within 30 days prior to study treatment initiation
• Other condition(s) that in the opinion of the investigator might compromise the objectives of the study or increase patient risk