Clinical Trial Results:
Repurposing disulfiram as treatment for metastatic colorectal cancer
An investigator initiated clinical phase II trial
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Summary
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EudraCT number |
2019-002748-25 |
Trial protocol |
DK |
Global end of trial date |
05 Aug 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Dec 2025
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First version publication date |
31 Dec 2025
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Other versions |
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Summary report(s) |
Synopsis_EudraCT 2019-002748-25 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
KFE19.17
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Odense Universitetshospital (OUH)
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Sponsor organisation address |
Kløvervænget 19, Odense C, Denmark, 5000
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Public contact |
PI Line Schmidt Tarpgaard, Department of Oncology, Odense Universitetshospital, +45 2251 1616, line.tarpgaard@rsyd.dk
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Scientific contact |
PI Line Schmidt Tarpgaard, Department of Oncology, Odense Universitetshospital, +45 2251 1616, line.tarpgaard@rsyd.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Aug 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jul 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Aug 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary objective:
Disease-control rate (complete response, partial response and/or stable disease >= 18 weeks
To investigate efficacy and safety of the treatment combination irinotecan, disulfiram and copper in patients with metastatic colorectal cancer having developed resistance to irinotecan.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki and GCP; all patients provided written informed consent, and all data were handled confidentially and pseudonymised in compliance with applicable data protection legislation.
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Background therapy |
All patients had previously received standard systemic therapy for metastatic colorectal cancer, including fluoropyrimidine-, oxaliplatin- and irinotecan-based regimens, with anti-EGFR or anti-VEGF antibodies when indicated. During the trial, patients were allowed best supportive care, but no concomitant anti-cancer systemic therapy was permitted. | ||
Evidence for comparator |
Not applicable – this was a single-arm, non-randomised phase II trial with no active or placebo comparator. | ||
Actual start date of recruitment |
01 Oct 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
9
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment took place from January 2020 to May 2022. Patients were recruited consecutively at Odense University Hospital, during routine outpatient visits and screened for eligibility as they developed irinotecan-resistant metastatic colorectal cancer. | ||||||||
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Pre-assignment
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Screening details |
Patients were screened for eligibility during routine outpatient visits. The treating oncologist identified potential candidates with irinotecan-resistant metastatic colorectal cancer and verified inclusion and exclusion criteria before obtaining written informed consent. | ||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||
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Arms
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Arm title
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Irinotecan + disulfiram + copper | ||||||||
Arm description |
Single treatment arm. Patients receive irinotecan 250 mg/m² as a 30-minute intravenous infusion every 3 weeks, with the possibility of intra-patient dose escalation if tolerated. Oral disulfiram and copper are given concomitantly according to the phase II schedule (disulfiram 400 mg/day plus copper 2 mg/day around the irinotecan infusion, followed by a lower maintenance dose of disulfiram in the second week of each cycle). Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Irinotecan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
250 mg/m² administered as a 30-minute intravenous infusion on day 1. every 3 weeks
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Investigational medicinal product name |
Disulfiram
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
400 mg orally once daily on days 1–7, followed by 100–400 mg orally once daily on days 8–14 of each 21-day cycle, given concomitantly with irinotecan and copper.
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Investigational medicinal product name |
Kobber
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
2 mg orally once daily on days 1–14 of each 21-day cycle, given concomitantly with disulfiram.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
Single treatment arm: irinotecan 250 mg/m² IV every 3 weeks with the option for intra-patient dose escalation, combined with continuous oral disulfiram and copper according to the phase II schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention-to-treat population
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who signed informed consent and received at least one cycle of study treatment. This set was used for all efficacy analyses, including disease-control rate, progression-free survival and overall survival.
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End points reporting groups
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Reporting group title |
Irinotecan + disulfiram + copper
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Reporting group description |
Single treatment arm. Patients receive irinotecan 250 mg/m² as a 30-minute intravenous infusion every 3 weeks, with the possibility of intra-patient dose escalation if tolerated. Oral disulfiram and copper are given concomitantly according to the phase II schedule (disulfiram 400 mg/day plus copper 2 mg/day around the irinotecan infusion, followed by a lower maintenance dose of disulfiram in the second week of each cycle). Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent. | ||
Subject analysis set title |
Intention-to-treat population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All patients who signed informed consent and received at least one cycle of study treatment. This set was used for all efficacy analyses, including disease-control rate, progression-free survival and overall survival.
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End point title |
Disease-control rate at 18 weeks [1] | |||||||||
End point description |
From date of inclusion until 18 weeks after inclusion.
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End point type |
Primary
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End point timeframe |
From date of inclusion until 18 weeks after inclusion.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a single-arm, non-comparative phase II trial. The primary end point (18-week disease-control rate) was summarised descriptively as a proportion in the intention-to-treat population, and no formal statistical hypothesis test was specified in the protocol. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Kaplan–Meier analysis of progression free survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Progression-free survival (PFS) was analysed in the intention-to-treat population using the Kaplan–Meier method. PFS was defined as the time from inclusion to radiological or clinical disease progression or death from any cause, whichever occurred first.
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan–Meier analysis of overall survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Overall survival (OS) was analysed in the intention-to-treat population using the Kaplan–Meier method. OS was defined as the time from inclusion to death from any cause. Patients alive at the time of analysis were censored at the date they were last known
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the first administration of irinotecan, disulfiram or copper until 28 days after the last dose of any study drug; serious adverse events considered related to study treatment were collected beyond this period if reported.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
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Reporting groups
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Reporting group title |
All treated patients
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Reporting group description |
Adverse events were collected from the first administration of study treatment until 28 days after the last dose of any study drug. Events were coded using MedDRA and graded according to NCI CTCAE version 5.0; relationship to study treatment was assessed by the investigator. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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12 Jul 2020 |
Due to unexpectedly high toxicity with continuous treatment with disulfiram and copper (in particular pronounced fatigue and neurological adverse events), the protocol was amended so that the dose and dosing schedule of disulfiram and copper were modified to a shorter, pulsed administration around the irinotecan infusion. The aim of this amendment was to reduce toxicity while maintaining the expected antitumour effect. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
