Partial Brain RT, Temozolomide, Chloroquine, and TTF Therapy for the Treatment of Newly Diagnosed Glioblastoma

• Histologically confirmed newly diagnosed grade IV glioma (gliosarcoma allowed)
• The subject must have recovered from the effects of surgery, postoperative infection, and other complications before enrollment. Post-operative unenhanced and contrast-enhanced MRI scan should be done within 72 hours after surgery. If it is not obtained within 72 hours post-resection, then an MRI obtained at least 2 weeks (or longer) after surgery is required
• Karnofsky performance status >= 70%
• Absolute neutrophil count >= 1,500/mm\^3 (=\< 21 days prior to registration)
• Platelets >= 100,000/mm\^3 (=\< 21 days prior to registration)
• Hemoglobin (Hgb) >= 9.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb >= 9.0 g/dL is acceptable.) (=\< 21 days prior to registration)
• Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula (=\< 21 days prior to registration)
• Total bilirubin =\< 1.5 times upper limit of normal (ULN) (=\< 21 days prior to registration)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =\< 1.5 times upper limit of normal (ULN) (=\< 21 days prior to registration)

• Female subjects of childbearing potential (i.e., those who are not postmenopausal for at least 1 year or surgically sterile by bilateral tubal ligation, bilateral oophorectomy or hysterectomy) and their male partners should practice at least one of the methods of birth control listed below during study entry, for the entire duration of the study and for at least 6 months after treatment with temozolomide and chloroquine:

  * A vasectomized male subject or a vasectomized partner of a female subject; hormonal contraceptives (oral, parenteral, or transdermal) for at least 3 months prior to study drug administration; intrauterine device (females); double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)

• Female subjects of child-bearing potential must have a negative pregnancy test (urine or serum) within 3 days of registration
• Must voluntarily sign and date informed consent form for study participation, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures

Exclusion Criteria:

• Gliomatosis cerebri (a diffuse glioma [usually astrocytic] growth pattern consisting of exceptionally extensive infiltration of a large region of the central nervous system, with involvement of at least 3 cerebral lobes, usually with bilateral involvement of the cerebral hemispheres and/or deep grey matter, and frequent extension to the brain stem, cerebellum, and even the spinal cord.)
• Recurrent glioblastoma (GBM)
• Metastatic GBM
• Infratentorial tumor
• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide. Implanted carmustine (BCNU) wafer is allowed
• Prior radiotherapy to the head or neck (except for T1 glottic cancer or nonmelanomatous skin cancer), resulting in overlap of radiation fields
• Any prior therapy for glioblastoma besides surgery (intra-operative techniques to guide resection and experimental imaging techniques are allowed). BCNU wafer is allowed
• Prior invasive malignancy (except for non-melanomatous skin cancer; carcinoma in situ (CIS) of the breast, CIS oral cavity, or CIS cervix, T1 glottic cancer) unless disease free for >= 5 years
• Prior, concomitant, or planned concomitant treatment with bevacizumab, carmustine implant (Gliadel) wafers or other intratumoral or intracavitary anti-neoplastic therapy, or other experimental therapeutics intended to treat the tumor; the exceptions are diagnostic and operative guides to improve extent of resection or imaging studies, quality of life, biomarker, or epidemiological studies
• History of hypersensitivity to temozolomide or excipients
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Lactating or pregnant female

• Severe, active, co-morbidity defined as follows:

  * Moderate or severe hepatic impairment (Child-Pugh category B or higher [score of 7 or higher ]); unstable angina and/or congestive heart failure within the last 6 months; transmural myocardial infarction within the last 6 months; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to enrollment; New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to enrollment

• History of stroke, cerebral vascular accident (CVA), or transient ischemic attack within 6 months (except if intra- or post-operative); serious and inadequately controlled cardiac arrhythmia; acute bacterial or fungal infection requiring intravenous antibiotics at the time of enrollment; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment; uncontrolled human immunodeficiency virus (HIV) with CD4 count \< 200; note, however, that HIV testing is not required for entry into this protocol
• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
• Subjects treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study, except intra-operative therapy to guide resection or experimental imaging without therapeutic intent
• Inability to undergo contrast-enhanced MRI scans
• Presence of implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, or other implanted electronic devices in the brain
• Documented clinically significant arrhythmia or severe ischemic heart disease
• Patients with underlying ocular disorders, including but not limited to: maculopathy, macular degeneration, and retinopathy