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).

Exclusion Criteria:

* Receipt of any other investigational agents within 14 days prior to study treatment
* Enrolled on another clinical trial testing a novel therapy or drug.
* History of allergic reaction to DSF or Cu.
* Treatment with the following medications are contraindicated with DSF when taken within 7 days prior to the first dose of DSF + Cu: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertaline, tindazole, tixanidine, atazanavir. (Note: the following medications are not contraindicated but should be cautioned if taking concurrently with DSF: warfarin, phenytoin, theophylline, chlorzoxazone, chlordiazepoxide, diazepam. If the patient is taking warfarin, INR should be monitored closely. If the patient has to remain on phenytoin, its serum concentration and response should be monitored closely.
* Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
* History of idiopathic seizure disorder, psychosis, or schizophrenia.
* History of Wilson's disease or family member with Wilson's disease.
* History of hemochromatosis or family member with hemochromatosis.
* Pregnant and breastfeeding women will be excluded because of the known teratogenic effect of RT and the unknown effect of TMZ and DSF on fetal development. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.