Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide

Glioblastoma Clinical Trial

Official title:

A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01907165
• Other study ID #: 201308038
• Status: Completed
• Phase: Early Phase 1
• Start date: October 10, 2013
• Est. completion date: February 9, 2018

Study information

• Verified date: July 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 9, 2018
• Est. primary completion date: November 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Temozolomide

• Disulfiram

Dietary Supplement:
• Copper gluconate

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacological effect of disulfiram in GBM patients	Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics	30 days
Secondary	Local tumor control probabilities	The Kaplan-Meier product-limit method will be used.	2 years
Secondary	Time to tumor progression	Modeled using the Cox proportional hazard models.	2 years

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine