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

Recurrent Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03034135
• Other study ID #: CAN-201
• Status: Completed
• Phase: Phase 2
• Start date: March 9, 2017
• Est. completion date: July 10, 2018

Study information

• Verified date: July 2019
• Source: Cantex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 10, 2018
• Est. primary completion date: July 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Drug:
• Disulfiram/Copper
Disulfiram/copper gluconate is taken three times a day.
• Temozolomide (TMZ)
TMZ is given per standard of care

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Lenox Hill Hospital	New York	New York
United States	Beaumont Hospital	Royal Oak	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Cantex Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

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