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

A Phase II, Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Efficacy of DIsulfiram and Copper Gluconate in Recurrent Glioblastoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: Disulfiram/Copper; Drug: Temozolomide (TMZ)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • New York
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • University of Cincinnati
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSF-Cu; Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months.	Drug: Disulfiram/Copper; Disulfiram/copper gluconate is taken three times a day.; Drug: Temozolomide (TMZ); TMZ is given per standard of care

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cantex Pharmaceuticals
• Investigators: Study Chair: Jiayi Huang, MD, Washington University School of Medicine in St. Louis

Publications and helpful links

General Publications

• Huang J, Chaudhary R, Cohen AL, Fink K, Goldlust S, Boockvar J, Chinnaiyan P, Wan L, Marcus S, Campian JL. A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma. J Neurooncol. 2019 May;142(3):537-544. doi: 10.1007/s11060-019-03125-y. Epub 2019 Feb 15.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Actual): July 10, 2018
• Study Completion (Actual): July 10, 2018

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 26, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Trace Elements; Micronutrients; Alcohol Deterrents; Acetaldehyde Dehydrogenase Inhibitors; Copper; Temozolomide; Disulfiram
• Other Study ID Numbers: CAN-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No