Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria

• •Diagnosis of GBM or its histological variants (WHO grade IV). Patients who are participating in the optional preoperative pharmacokinetic study, may have presumed GBM based on clinical/radiological findings. However, patient must have histologically confirmed GBM before continuing to receive DSF with concurrent RT/TMZ.
• •Expansion Cohort: must have a diagnosis of GBM (or its histological variants) with IDH, BRAF, or NF1 mutations. Confirmation of these mutations may be either by immunohistochemistry or next-generation sequencing
• •At least 18 years of age.
• •Karnofsky performance status (KPS) of at least 60%
• •For patients who will participate in the optional pre-operative DSF pharmacokinetic study, they should be eligible for surgical resection for which at least 0.2 cubic cm or approximately 200 mg of tumor will be removed in additional to tumor specimen required for pathology evaluation. Patients enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.
• •Eligible for and planning to receive standard fractionated RT with concurrent TMZ.
• •Willing to remain abstinent from consuming alcohol while on DSF.
• •Willing to defer definitive surgery for one week while taking DSF and Cu. Patients who declined the optional pre-operative pharmacokinetic study or enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.
• •Meets the following laboratory criteria:
• •* Absolute neutrophil count ≥ 1,500/mcL
• •* Platelets ≥ 100,000/mcL
• •* Hemoglobin \> 10.0 g/dL (transfusion and/or ESA allowed)
• •* Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
• •* AST and ALT \< 3 x ULN
• •* Serum creatinine \< 1.5 x ULN or creatinine clearance \> 50 mL/min (by Cockcroft-Gault)
• •Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• •Able to take oral medication.
• •Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).