Clinical trial NCT01907165: Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide
Official title: A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Glioblastoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2013-07-24
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacological effect of disulfiram in GBM patients
timeFrame: 30 days
Secondary outcomes:
measure: Local tumor control probabilities
timeFrame: 2 years
measure: Time to tumor progression
timeFrame: 2 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jiayi Huang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097. No abstract available.