Temozolomide, Memantine Hydrochloride, Mefloquine, and Metformin Hydrochloride in Treating Patients With Glioblastoma Multiforme After Radiation Therapy

Inclusion Criteria:

* Patients with histologically proven supratentorial glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV astrocytoma) will be eligible for this protocol; patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made prior to any definitive treatment (radiotherapy, chemotherapy)
* All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must be registered prior to treatment with study drug
* Patients must have a Karnofsky performance status (KPS) of \>= 60
* White blood cells (WBC) \>= 3,000/ul (performed within 14 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (performed within 14 days prior to registration)
* Platelet count of \>= 100,000/mm\^3 (performed within 14 days prior to registration)
* Hemoglobin \>= 10 gm/dl (eligibility level for hemoglobin may be reached by transfusion) (performed within 14 days prior to registration)
* Serum glutamic oxaloacetic transaminase (SGOT) \< 2 times upper limit of normal (ULN) (performed within 14 days prior to registration)
* Bilirubin \< 2 times ULN (performed within 14 days prior to registration)
* Creatinine \< 1.5 mg/dL (performed within 14 days prior to registration)
* For patients on mefloquine arm, a baseline electrocardiogram (EKG) without evidence of prolonged corrected QT (QTc) interval \> 450 ms or clinically significant arrhythmia must be obtained within 14 days prior to registration
* A brain scan should be performed within 14 days prior to registration and steroid dosing should be stable or decreasing for at least 5 days; if the steroid dose is increased between the date of imaging and registration a new baseline magnetic resonance (MR)/computed tomography (CT) is required; the same type of scan, i.e., magnetic resonance imaging (MRI) or CT must be used throughout the period of protocol treatment for tumor measurement
* Patients must have completed standard radiation therapy with concurrent TMZ and must not have evidence of progressive disease on post treatment imaging
* Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (B-HCG) pregnancy test documented within 72 hours of start of therapy
* Patients must be registered on the study within 5 weeks of completion of concurrent chemoradiation

Exclusion Criteria:

* Patients must not have 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
* For mefloquine arm, patients with evidence of QTc interval \> 450 ms or clinically significant arrhythmia on baseline EKG obtained within 14 days of registration will be ineligible for protocol enrollment
* Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years, are ineligible
* Patients must not have active infection or serious intercurrent medical illness
* Patients must not be pregnant/breast feeding and must agree to practice adequate contraception (acceptable forms of birth control include condom with spermicide and/or diaphragm with spermicide, and non-barrier contraception such as tubal ligation, vasectomy, oral contraceptives, implanted levonorgestrel, vaginal hormonal contraceptive ring)
* Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism; patients with a history of psychosis/schizophrenia or cardiac disease requiring beta-blocker treatment (unable to change medication to non-beta blocker), anti-malarial drugs, or quinine or quinidine will not be eligible for enrollment to a mefloquine containing arm; patients who are on active treatment with one of the study drugs at the time of evaluation will not be eligible for enrollment to an arm containing that study drug
* For mefloquine arm, patients must not be on enzyme inducing anticonvulsants (EIAED); if the treating physician elects to change the medication to a non-enzyme inducing agent, a 2-week wash out period will be required after stopping EIAED prior to initiation of treatment