Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Glioblastoma in the Adjuvant or Recurrent Setting

General Inclusion Criteria:

* Patient must willingly provide written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
* Patients must be ≥ 18 years old.
* Patients must have histologically confirmed initial diagnosis of primary intracranial WHO Grade IV malignant glioma (glioblastoma).
* Patients must have preliminary GBM MGMT status (tumor must be MGMT promoter unmethylated) determined prior to study entry. If initial MGMT status is determined to be "unmethylated", by an outside institution the patient may be enrolled and begin treatment. However, MGMT status must be retested following enrollment by central laboratory CLIA certified testing at MD Anderson.
* Patients must have Karnofsky Performance Status (KPS) \> 60% (i.e., 70, 80, 90 or 100).
* Adequate recovery from all recent surgery is required. At least 21-days must have elapsed from the time of any major surgery, including craniotomy/tumor resection. Patients must have recovered from all surgery-related toxicities to Grade 1 or less.
* Prior therapy with gamma knife or other focal high-dose radiation is allowed, but at least 2 weeks must have elapsed from the time of treatment, and the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field.
* Patients having prior therapy with Laser Induced Thermal Therapy (LITT) is allowed, but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence
* Patients must be at least 4 weeks from last dose of chemotherapy.
* Patients must have recovered from all treatment-related toxicities to Grade 1 or less.
* If receiving corticosteroids, patients must be on a stable or decreasing dose of corticosteroids for ≥ 5 days prior to baseline MRI.
* Patients must have a predicted life expectancy of at least 12 weeks.
* Patients must have adequate bone marrow and organ function.
* Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up after treatment termination.
* If the patient has been using the Optune™ device, it will be discontinued before initiating treatment with either study medication, and per inclusion criterion listed above, the patient must have recovered from all treatment-related toxicities to Grade 1 or less.
* Pregnancy restrictions - Women of childbearing potential must have a negative B-HCG documented within 7 days prior to registration

Group Specific Inclusion Criteria - Recurrent GBM (Group 1):

* Patients must have recurrent disease whose initial diagnostic pathology confirmed glioblastoma will not need re-biopsy. Alternately, patients with prior intracranial low-grade glioma or anaplastic glioma will be eligible, if histologic assessment demonstrates transformation to GBM (first diagnosis of secondary GBM).
* Patients must have radiographic evidence of recurrent/progressive GBM after prior therapy (biopsy or resection and chemoradiation); 1st recurrence of GBM only, per RANO criteria. Histologically documented transformation from a lower grade gliomas will be considered first recurrence.
* Patients must be \>12 weeks from radiotherapy, to minimize the potential for MRI changes related to treatment (pseudoprogression) that might be misdiagnosed as true progression of disease, unless the patient fulfills criteria for early progressive disease by RANO.
* Patients must have been previously treated for GBM with concurrent temozolomide and radiation followed by adjuvant temozolomide chemotherapy.
* Patients must be at least 4 weeks or 5 half-lives (whichever is shorter) from the last dose of prior investigational anti-cancer drugs.

Group Specific Inclusion Criteria - Newly Diagnosed GBM requiring maintenance therapy (Group 2)

* Patients must not have recurrent disease.
* Patients must be \< 6 weeks from radiotherapy to start of treatment with VAL-083.
* Patients must have been previously treated for GBM with concurrent temozolomide and radiation, and received no subsequent maintenance temozolomide chemotherapy.
* No prior investigational agent.

Exclusion Criteria:

* Within 12 weeks of chemoradiation unless the patient fulfills criteria for early progressive disease by RANO, for Group 1; and, more than 6 weeks from chemoradiation for Group 2.
* Receipt of investigational agents within 5 half-lives of last dose of investigational agent.
* Concurrent use of other investigational agents or Optune™ device
* Prior therapy with lomustine.
* Prior therapy with bevacizumab.
* Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the Sponsor.
* Evidence of leptomeningeal spread of disease.
* Need for urgent palliative intervention (e.g., impending herniation).
* Severe, intercurrent illness including, but not limited to unstable systemic disease, including ongoing or active infection, uncontrolled hypertension, serious cardiac arrhythmia requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with a known sensitivity to any of the products to be administered during treatment.
* Patients unable to undergo MRI of the brain.
* Women who are pregnant or lactating. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment.