Phase II Open Labeled Trial of Disulfiram with Copper in Metastatic Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Univerzita Palackeho V Olomouci

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2019 → 12 Sep 2024

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514665-19-00

EudraCT number

2016-001386-81

ClinicalTrials.gov

NCT03323346

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic

To evaluate the efficacy of the treatment by assessment of clinical response rate (RR) and clinical benefit rate (CBR)

Secondary objectives 5

1. To evaluate the efficacy of the treatment by assessment of time to progression (TTP)
2. To evaluate the efficacy of the treatment by assessment of overall survival (OS)
3. To determine pharmacokinetic parameters for disulfiram and its active metabolites administered in combination with copper supplements in cancer patient population
4. To describe safety profile of disulfiram administered in combination with copper supplements
5. Parallel analysis to assess (identify) potential candidate surrogate biomarkers of disulfiram efficacy, as well as identification (using proteomic, biochemical and molecular genetic studies) of potential predictive biomarkers of disulfiram sensitivity or resistance will be performed. Surrogate biomarker analysis will focus on in vivo ubiquitin-proteosomal system inhibition, cell cycle and DNA damage

Conditions and MedDRA coding

metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patients with stage IV breast cancer with metastases demonstrated by appropriate imaging techniques (CT, PET or PET/CT, MRI, ultrasound, etc.)
2. Histologically or cytologically confirmed tumor
3. Age of 18 years or more
4. ECOG performance status of 0 - 2
5. Patients have failed, intolerated or refused standard therapeutic modalities or for whom other systemic therapies are not an option
6. Not received systemic anticancer therapy or radiation or had major surgery in last 2 weeks
7. Not currently participating in another study
8. Anticipated survival of at least 2 months
9. Baseline AST and ALT not greater than 2.5 X upper institutional limit for patient without liver metastasis / not greater than 5.0 X upper institutional limit for patient with liver metastasis
10. Serum copper less than 40 μmol/l
11. Serum ceruloplasmin > 17 mg/dL but not greater than 2.5 X upper institutional limit
12. Able and willing to sign informed consent and to comply with study procedures
13. Able to ingest oral medications
14. No known allergy to disulfiram or copper
15. Willing to refrain from ingestion of alcoholic beverages while on the study

Exclusion criteria 15

1. Participation in another clinical trial of a therapeutic drug during the past 14 days
2. Addiction to alcohol or drugs
3. Baseline AST or ALT greater than 2.5 X upper institutional limit for patient without liver metastasis / greater than 5.0 X upper institutional limit for patient with liver metastasis
4. Unable to ingest oral medications
5. Unable to undergo CT/SPECT scanning because of inability to lie recumbent in the scanner
6. Actively receiving cytotoxic cancer chemotherapy agents
7. Anticipated survival of less than 2 months
8. Women of child-bearing potential who are not using a commonly accepted effective means of contraception; women of child-bearing potential had positive pregnancy test before enrollment; the pregnancy test was used more than 7 days before screening visit date
9. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology, toxic hepatitis, or cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper institutional limit
10. History of Wilson's disease or family member with Wilson's disease
11. History of iron overload syndrome, hemochromatosis or family member with hemochromatosis
12. Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram
13. Pregnant women and nursing mothers are not allowed to enroll on this study
14. Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives
15. Patients who are taking cannabis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. effect of treatment with disulfiram and copper on clinical response rate (RR, percentage of patients whose cancer shrinks; termed a partial response, PR; or disappears after treatment; termed a complete response, CR; RR=PR+CR)
2. effect of treatment with disulfiram and copper on clinical benefit rate (CBR=CR+PR+SD, where SD is defined as a stable disease - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for minimum 6-8 weeks)

Secondary endpoints 6

1. Time to progression (TTP)
2. Overall survival (OS)
3. Pharmacokinetic - Total exposure (AUC0-τ)
4. Pharmacokinetic - Maximum plasma concentrations (Cmax)
5. Pharmacokinetic - Minimum plasma concentration (Cmin)
6. Safety outcome measures - Nature, frequency, and severity of adverse events as graded using Common Terminology Criteria for Adverse Events (CTCAE), v5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Univerzita Palackeho V Olomouci

Sponsor organisation

Univerzita Palackeho V Olomouci

Address

Krizkovskeho 511/8

City

Olomouc

Postcode

779 00

Country

Czechia

Scientific contact point

Organisation

Univerzita Palackeho V Olomouci

Contact name

Marian Hajduch

Public contact point

Organisation

Univerzita Palackeho V Olomouci

Contact name

Marian Hajduch

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications