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

• Sponsor: Cantex Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03034135
• Collaborator: (none)
• Enrollment: 23
• Locations: 8
• Arm: 1
• Actual Duration (Months): 16
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Glioblastoma	Drug: Disulfiram/Copper; Drug: Temozolomide (TMZ)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 9, 2017
• Actual Primary Completion Date: Jul 10, 2018
• Actual Study Completion Date: Jul 10, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Progression Free Survival [6 months]

   Percentage of patients that are free from progressive disease per RANO criteria

2. Overall Survival [6 months and 12 months]

   Percentage of patients that are alive

3. Number of Participants With Serious Adverse Events [14 months]

   Number of Participants with Grade 3 and 4 serious adverse events

4. Median Progression Free Survival [12 months]

   Duration of progression free survival according to RANO criteria

5. Median Duration of Overall Survival [14 months]

   Duration of overall survival for patients that are alive

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

• 1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beaumont Hospital	Royal Oak	Michigan	United States	48073
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	John Theurer Cancer Center	Hackensack	New Jersey	United States	07601
4	Lenox Hill Hospital	New York	New York	United States	10075
5	University of Cincinnati	Cincinnati	Ohio	United States	45220
6	Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37212
7	Baylor University Medical Center	Dallas	Texas	United States	75246
8	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112-5550

Sponsors and Collaborators

• Cantex Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 28, 2016

More Information

Publications

None provided.

• Responsible Party: Cantex Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03034135
• Other Study ID Numbers: CAN-201
• First Posted: Jan 27, 2017
• Last Update Posted: Sep 13, 2021
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioblastoma; Recurrence; Copper; Temozolomide; Disulfiram

Study Results

Participant Flow

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Period Title: Overall Study
STARTED	23
COMPLETED	21
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Disulfiram and Copper Gluconate
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Overall Participants	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	7 30.4%
Male	16 69.6%
Race/Ethnicity, Customized (Count of Participants)
White	21 91.3%
Black	1 4.3%
Other	1 4.3%
Region of Enrollment (Count of Participants)
United States	23 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	21
Complete response	0 0%
Partial Response	0 0%

2. Secondary Outcome

Title	Progression Free Survival
Description	Percentage of patients that are free from progressive disease per RANO criteria
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	14 60.9%

3. Secondary Outcome

Title	Overall Survival
Description	Percentage of patients that are alive
Time Frame	6 months and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	21
6 months	61 265.2%
12 months	35 152.2%

4. Secondary Outcome

Title	Number of Participants With Serious Adverse Events
Description	Number of Participants with Grade 3 and 4 serious adverse events
Time Frame	14 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	23
Count of Participants [Participants]	2 8.7%

5. Secondary Outcome

Title	Median Progression Free Survival
Description	Duration of progression free survival according to RANO criteria
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	21
Median (95% Confidence Interval) [months]	1.7

6. Secondary Outcome

Title	Median Duration of Overall Survival
Description	Duration of overall survival for patients that are alive
Time Frame	14 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DSF-Cu
Arm/Group Description	Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day. Temozolomide (TMZ): TMZ is given per standard of care
Measure Participants	21
Median (95% Confidence Interval) [months]	7.1

Adverse Events

Time Frame	14 months
Arm/Group Title	Group A
Arm/Group Description	Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ.
All Cause Mortality
	Group A
	Affected / at Risk (%)	# Events
Total	14/23 (60.9%)
Serious Adverse Events
	Group A
	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)
General disorders
Fatigue	1/23 (4.3%)	1
Hepatobiliary disorders
Hepatobiliary disorders	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Group A
	Affected / at Risk (%)	# Events
Total	0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.