Study of Marizomib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Brain Cancer

Inclusion Criteria:

* Signed Informed Consent Form
* Males and females of age ≥ 18 years or of age ≥ 22 years for those assigned to Optune™ at the time of signing of the informed consent document.
* Histologically confirmed newly diagnosed G4 MG
* Karnofsky Performance Status (KPS) score ≥ 70%
* For Concomitant Treatment: Prior tumor resection or biopsy up to 8 weeks prior to first MRZ dose
* For Adjuvant Treatment: All AEs resulting from surgery must have resolved to NCI-CTCAE (v. 4.03) Grade ≤ 1
* Stable or decreasing dose of corticosteroids over 14 days prior to first MRZ dose
* For Concomitant Treatment: No prior treatment with MRZ or any other PIs, including BTZ, carfilzomib (CFZ), or ixazomib (IXZ)
* For Adjuvant Treatment: No prior treatment with BTZ, CFZ, or IXZ
* No investigational agent within 4 weeks prior to first dose of study drug
* Adequate hematological, renal, and hepatic function
* Patients must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with AEDs must be on stable doses for at least 14 days prior to enrollment
* Absence of known HIV infection, chronic hepatitis B, or hepatitis C infection; absence of any other serious medical condition which could interfere with oral medication intake
* Patients with archival tumor tissue suitable for measurement of proteasome activity and biomarker status must give permission to access and test the tissue. Patients without archival tumor tissue are eligible for the Dose-Escalation stage, but not the Dose-Expansion stage of the study
* For women of child-bearing potential and for men with partners of child-bearing potential, patient must agree to take contraceptive measures for duration of treatments and for one month after last study treatment
* Willing and able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

* Co-medication or concomitant therapy that may interfere with study results
* History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months
* Other chemotherapy or anti-tumor treatment for brain tumor (other than therapies required by the inclusion criteria of this protocol)
* Pregnant or breast feeding
* Uncontrolled intercurrent illness that would limit compliance with study requirements, or disorders associated with significant immunocompromised state
* Known other previous/current malignancy requiring treatment within ≤ 3 years except for liited disease treated with curative intent
* Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medial Monitor
* For those enrolled in Adjuvant Treatment with Optune™, patients are excluded if they are \< 22 years of age, have an active implanted medical device, a skull defect, bullet fragments in the head, sensitivity to conductive hydrogels, a scalp condition that might interfere with wearing the device, or GBM that is not supratentorial.