Inclusion Criteria:
1. Confirmed recurrent gliomas that were originally diagnosed as high-grade glioma (World Health Organization \[WHO\] Grade 3 or 4; astrocytoma, oligodendroglioma, or glioblastoma) by histopathology or molecular studies.
2. Progressive or recurrent gliomas documented by magnetic resonance imaging (MRI) no earlier than 180 days after first surgery for gliomas and no earlier than 90 days after completion of radiotherapy (applies to patients with first progression/recurrence only).
3. Patients must have medical records available documenting known histology or molecular and genetic information resulting from prior analyses, or tumor tissue samples available from prior glioma surgery or open biopsy for correlative research.
4. For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI as per the RANO criteria within 28 days prior to the first dose. These patients must have at least one measurable lesion per RANO.
5. No more than two prior lines of therapy for high-grade glioma (WHO Grade 3 or 4). The first-line therapy must include radiotherapy (minimum of 50 Gy; 34 Gy in elderly patients) with concomitant or adjuvant standard chemotherapy (temozolomide (TMZ), or procarbazine, lomustine and vincristine in patients with anaplastic oligodendroglioma).
6. Eastern Cooperative Oncology Group (ECOG) performance status \<2.
7. Full recovery (grade ≤1) from the toxic effects of any earlier intervention and a minimum of 28 days from the last administration of any investigational agent that has not received regulatory approval for any indication at the time of registration.
8. Adequate renal, liver and bone marrow function without packed red blood cell/platelet transfusions within 4 weeks of the date of lab test during screening:
* Leukocytes ≥3.0 × 10\^9/L
* Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
* Platelets ≥100 × 10\^9/L
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin ≤1.5 × upper limit of normal (ULN), unless documented Gilbert's syndrome.
* Aspartate transaminase/alanine transaminase ≤2.5 × ULN
* Creatinine clearance ≥60 mL/min calculated as per Cockcroft-Gault equation.
9. Patients must be ≥18 years of age.
10. Life expectancy (as assessed by the Investigator) at least three months.
11. Patients must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications.
12. Have provided written informed consent.
13. Patients must be willing to have multiple blood draws for PK analysis.
14. Female patients, of childbearing potential, must have a negative serum pregnancy test within 7 days prior to study treatment initiation and agree to use adequate contraception or practice sexual abstinence as the preferred and usual lifestyle of the patient during the study and for up to 120 days (4 months) after the last dose of study treatment.
15. Male patients with female partners of childbearing potential must, even if surgically sterilized, agree to practice effective barrier contraception and practice true abstinence.
16. Human immunodeficiency virus infected patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to study registration are eligible for this trial.
Exclusion Criteria:
1. Prior malignancy (other than glioma) expected to require treatment within a 6-month period (except adequately treated basal cell carcinoma of the skin). Patients who had another malignancy in the past but have been free of active disease for more than 2 years, are eligible.
2. Have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study registration.
3. Have received chemotherapeutic agents (including TMZ) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study registration.
4. Serious concomitant systemic disorders, for example, abnormal electrocardiogram (ECG) indicative of cardiac disease (patients with Fridericia-corrected QT interval \[QTcF\] \>480 msec.
5. Patients with abnormal sodium, potassium, or creatinine levels grade ≥2.
6. Inability to comply with protocol or study procedures.
7. Women who are pregnant or breastfeeding.
8. Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis.
9. Patients completing radiotherapy treatment less than 2 weeks prior to planned study treatment initiation.
