Safety, Tolerability and Efficacy of Disulfiram and Copper Gluconate in Recurrent Glioblastoma

Phase 2

Completed

• Conditions: Recurrent Glioblastoma
• Interventions: Drug: Disulfiram/Copper; Drug: Temozolomide (TMZ)

• Registration Number: NCT03034135
• Lead Sponsor: Cantex Pharmaceuticals

Brief Summary

This study of DSF-Cu in combination with TMZ for recurrent GBM will evaluate the antitumor effect in patients who have recurrent GBM. Patients will take DSF-Cu daily during their routine standard of care with TMZ therapy for approximately 6 months. Patients will be evaluated for response every 8 weeks. Patients will be followed up 2 years after the last dose of DSF-Cu.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-01-25
• Study First Submitted QC: 2017-01-26
• Study First Posted: 2017-01-27
• Study Start: 2017-03-09
• Primary Completion: 2018-07-10
• Study Completion: 2018-07-10
• Status Verified: 2019-07
• Disposition First Submitted: 2019-07-23
• Results First Submitted: 2021-04-02
• Results First Submitted QC: 2021-08-17
• Disposition First Submitted QC: 2021-08-17
• Last Update Submitted: 2021-08-17
• Results First Posted: 2021-09-13
• Disposition First Posted: 2021-09-13
• Last Update Posted: 2021-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Histologically confirmed GBM (WHO grade IV).
• The subject must have completed RT with concurrent TMZ at least 12 weeks prior to the planned start of treatment on this study UNLESS there is pathological verification of recurrent tumor and at least 4 weeks have elapsed since the end of RT with concurrent TMZ.
• Experienced first unequivocal progression of tumor by magnetic resonance imaging (MRI) [as assessed via Radiologic Assessment in Neuro-Oncology (RANO) criteria within 3 months from the last dose of TMZ.
• Karnofsky performance status (KPS) of at least 60%.
• Willing to remain abstinent from consuming alcohol.
• Recovered from the toxic effects of prior therapy to < grade 2 toxicity per NCI CTCAE prior to study registration (except lymphopenia).
• Meets laboratory criteria for the following parameters: ANC, platelets, hemoglobin, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, BUN and creatinine.
• 11. Females of childbearing potential must be willing to use an acceptable method of birth control (i.e., intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

Exclusion Criteria

• Radiographic evidence of leptomeningeal dissemination, gliomatosis cerebri, infratentorial tumor, or disease at sites remote from the supratentorial brain.
• Enrolled in another clinical trial testing a novel therapy or drug within the past 4 weeks.
• Received more than one course of radiation therapy or more than a total dose of 75 Gy.
• History of allergic reaction/hypersensitivity to temozolomide, dacarbazine, DSF or Cu.
• Treatment with the following medications are contraindicated with DSF: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertraline, tindazole, tizanidine, atazanavir.
• Fever within 3 days prior to study enrollment.
• Active or severe hepatic or renal disease.
• Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE
• History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications.
• History of Wilson's disease.
• History of hemochromatosis.
• Pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DSF-Cu	Disulfiram/Copper	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months.
DSF-Cu	Temozolomide (TMZ)	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	6 months	ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	6 months	Percentage of patients that are free from progressive disease per RANO criteria
Number of Participants With Serious Adverse Events	14 months	Number of Participants with Grade 3 and 4 serious adverse events
Median Duration of Overall Survival	14 months	Duration of overall survival for patients that are alive
Overall Survival	6 months and 12 months	Percentage of patients that are alive
Median Progression Free Survival	12 months	Duration of progression free survival according to RANO criteria

Trial Locations

Locations (8)

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

John Theurer Cancer Center; 🇺🇸 Hackensack, New Jersey, United States

Vanderbilt Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

Lenox Hill Hospital; 🇺🇸 New York, New York, United States