Glioblastoma
Conditions
Brief summary
This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients.
Interventions
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of histologically confirmed GBM (WHO grade IV). * At least 18 years of age. * ECOG performance status of at least 2. * Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gy with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy). * Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide. * Willing to remain abstinent from consuming alcohol while on disulfiram. * Meets the following laboratory criteria: * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin \> 9.0 g/dL (transfusion and/or ESA allowed) * Total bilirubin ≤ 2x institutional upper limit of normal (ULN) * AST and ALT \< 3 x ULN * Calculated creatinine clearance must be \> 60 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 enrollment. * Enrolled on another clinical trial testing a novel therapy or drug. * History of allergic reaction to disulfiram. * Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram. * Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) Class III or IV heart failure (Appendix B), 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. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacological effect of disulfiram in GBM patients | 30 days | Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local tumor control probabilities | 2 years | The Kaplan-Meier product-limit method will be used. |
| Time to tumor progression | 2 years | Modeled using the Cox proportional hazard models. |
Countries
United States
Outcome results
None listed