Metastatic, non-resectable and irinotecan-resistant colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Disulfiram
Product Name: disulfiram
Pharmaceutical Form: Effervescent tablet
INN or Proposed INN: DISULFIRAM
CAS Number: 97-77-8
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Department of Oncology, Odense Universitetshospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -- Age = 18 years. - Histologically verified colorectal adenocarcinoma. - Non-resectable mCRC. - Measurable or no-measurable disease according to RECIST version 1.1. - Performance status (WHO) of 0-1 and a life expectancy > 3 months. - Documented early* progressive disease following at least 2months of irinotecan (+/-fluoropyrimidines). **on treatment or within 6 mons after ended treatment. - Adequate haematological function defined as neutrophils ? 1.5 x 109/l and platelets = 100 x 109/l. - Adequate organ function (normal bilirubin, GFR (may be calculated) > 60 ml/min). - Willingness to refrain from alcohol consumption of alcohol during the trial and 14 days after the last treatment with Disulfiram. - Woman of childbearing potential must have been tested negative in a serum pregnancy test within 5 days prior to randomisation. Male and female patients who have the potential to reproduce must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) during the study and for 6 months after the discontinuation of study medication. - Has provided written informed consent prior to performance of any study procedure. - Written informed consent must be obtained according to the local Ethics Committee requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: - Known UGT-1A1 polymorphism. - Known CNS metastases - Prior history of cancer, except cervix in situ carcinoma, in situ urothelial carcinoma or previously treated and cured skin basocellular, and any other cancer in complete remission for at least 2 years. - Uncontrolled hypertension (systolic blood pressure > 169 mmHg or diastolic blood pressure > 100 mmHg) - Any other condition or therapy, which in the investigator’s opinion may pose a risk to the patient or interfere with the study objectives (e.g. known CNS metastasis; infection; drainage of ascites or pleural effusion within 4 weeks; intestinal obstruction; uncontrolled diabetes; AMI within 12 months; severe/unstable angina; known HIV or hepatitis B or C; major surgery within 4 weeks; uncontrolled hypertension). - Known allergy or intolerance to any of the drugs used (irinotecan, disulfiram, and copper).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: Secondary objectives: ?Progression-free survival (PFS) ?Overall survival (OS) ?Response rate (RR) according to RECIST criteria version 1.1 ?Toxicity ?EORTC QLQ-C30 ?Correlation between tumor markers and outcome ;Primary end point(s): Primary objective: ?Disease-control rate (complete response, partial response and/or stable disease >= 18 weeks ;Timepoint(s) of evaluation of this end point: We will treat the first 3 patients with a lower dose of disulfiram (200 mg/day) before we start to use the planned optimal dose of disulfiram (400 mg/day). Patients 1-3 Copper 2 mg/day + disulfiram 200 mg/day + irinotecan 250 mg/m2 every 3 weeks with the opportunity for doses escalation of irinotecan in the subsequent series. If no patient experience severe toxicity the next patients will receive disulfiram 400 mg/day Patients 4-6 Copper 2 mg/day + disulfiram 400 mg/day + irinotecan 250 mg/m2 every 3 weeks with the opportunity for doses escalation of irinotecan in the subsequent series. If no patient experience severe toxicity, we will include further 22 patients at this dose level. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary objectives: ? Progression-free survival (PFS) ? Overall survival (OS) ? Response rate (RR) according to RECIST criteria version 1.1 ? Toxicity ? EORTC QLQ-C30 ? Correlation between tumor markers and outcome ;Timepoint(s) of evaluation of this end point: We will treat the first 3 patients with a lower dose of disulfiram (200 mg/day) before we start to use the planned optimal dose of disulfiram (400 mg/day). Patients 1-3 Copper 2 mg/day + disulfiram 200 mg/day + irinotecan 250 mg/m2 every 3 weeks with the opportunity for doses escalation of irinotecan in the subsequent series. If no patient experience severe toxicity the next patients will receive disulfiram 400 mg/day Patients 4-6 Copper 2 mg/day + disulfiram 400 mg/day + irinotecan 250 mg/m2 every 3 weeks with the opportunity for doses escalation of irinotecan in the subsequent series. If no patient experience severe toxicity, we will include further 22 patients at this dose level. | — |
Countries
Denmark
Contacts
Public ContactPI Line Schmidt Tarpgaard
Department of Oncology, Odense Universitetshospital
Outcome results
None listed