Disulfiram + Chemotherapy for Pancreatic Cancer

No longer recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Phenytoin, others

Disqualifiers: Brain metastases, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 4-5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding disulfiram, a drug commonly used to treat alcohol dependence, to chemotherapy can help treat pancreatic cancer that has spread or other solid tumors unresponsive to treatment. Researchers aim to determine if disulfiram can reduce cancer-related muscle loss and enhance chemotherapy effectiveness. One group of participants will receive the chemotherapy drug gemcitabine with disulfiram, while another group will receive disulfiram with chemotherapy selected by their doctor. The trial seeks participants with metastatic pancreatic cancer or other solid tumors not responding to current treatments, particularly those experiencing cancer-related weight loss affecting daily life. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are receiving other chemotherapy, immunotherapy, or investigational treatments. You also cannot take phenytoin or consume alcohol during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that disulfiram, initially used to treat alcoholism, is safe for cancer treatments. Studies found that combining disulfiram with other cancer drugs does not cause serious side effects and may extend patient survival.

Gemcitabine hydrochloride, a chemotherapy drug for pancreatic cancer, has been shown in past research to be generally safe and well-tolerated by patients. It has served as a standard treatment to improve survival rates in some cancers.

Both treatments have been safely used in people before, and researchers are studying their combined effectiveness further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for pancreatic cancer, which typically includes chemotherapy treatments like FOLFIRINOX or nab-paclitaxel with gemcitabine, the study treatment combines disulfiram, a drug traditionally used to treat alcohol dependence, with chemotherapy. Researchers are excited about this approach because disulfiram may disrupt cancer cell survival pathways, potentially enhancing the effects of chemotherapy. This combination could offer a new way to target pancreatic cancer cells more effectively, possibly improving patient outcomes beyond what current chemotherapy regimens achieve.

What evidence suggests that disulfiram and chemotherapy could be effective for metastatic pancreatic cancer?

Research has shown that disulfiram might enhance the effectiveness of chemotherapy against cancer. In this trial, participants in Cohort I will receive a combination of gemcitabine hydrochloride and disulfiram, while those in Cohort II will receive chemotherapy, as determined by the treating oncologist, along with disulfiram. Disulfiram has shown promise in reducing muscle loss caused by tumors, which is crucial for patients with advanced cancer. Studies have also found that disulfiram can make cancer cells more responsive to treatments like gemcitabine, a chemotherapy drug. Additionally, disulfiram can initiate processes in the body that combat cancer cells. Early findings suggest that when combined with chemotherapy, disulfiram could improve treatment outcomes for pancreatic cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Aminah Jatoi, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that are untreatable by standard methods or metastatic pancreatic cancer. Participants must have acceptable blood counts, organ function, and be able to take oral medication. Women of childbearing potential must use effective contraception and not be pregnant or nursing. People can't join if they have curative treatment options available, uncontrolled illnesses, untreated brain metastases, certain neuropathy levels, or are using specific drugs like phenytoin.

Inclusion Criteria

Your bilirubin levels are not more than twice the normal limit.

Ability to provide written informed consent

You are expected to live for at least 12 more weeks.

Exclusion Criteria

You cannot stop drinking alcohol during the study.

Pregnant women

I have moderate to severe numbness or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive gemcitabine hydrochloride IV and disulfiram orally for 28 to 35 days

4-5 weeks

3 visits (in-person) for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person), followed by every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Disulfiram
• Gemcitabine Hydrochloride

Trial Overview The study is testing the combination of Disulfiram (a drug potentially preventing muscle wasting) with chemotherapy (Gemcitabine Hydrochloride) in patients whose cancers haven't responded to other treatments. The goal is to find the safest dose of Disulfiram and see if it enhances chemotherapy's effectiveness while reducing muscle loss associated with cancer.

How Is the Trial Designed?

Group I: Cohort II (chemotherapy and disulfiram) Experimental Treatment 3 Interventions

Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35.

Group II: Cohort I (gemcitabine hydrochloride and disulfiram) Experimental Treatment 3 Interventions

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and disulfiram PO on days 1-28 or days 1-35.

Disulfiram is already approved in United States, European Union for the following indications:

Approved in United States as Antabuse for:

• Alcohol dependence

Approved in European Union as Antabuse for:

• Alcohol dependence

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37293156/

Disulfiram combined with chemoimmunotherapy ... Disulfiram combined with chemoimmunotherapy potentiates pancreatic cancer treatment efficacy through the activation of cGAS-STING signaling ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2590156724000793

Disulfiram and cancer immunotherapy: Advanced nano ... Disulfiram has been found to be effective in tumor treatment. Despite the promising results observed in preclinical and early clinical studies, the use of ...

3. gutnliver.org gutnliver.org/journal/view.html?pn=ahead&uid=2314&vmd=Full

Disulfiram/Copper Complex Induces Cytotoxicity in ... Results: We demonstrated that DSF/Cu effectively induced cytotoxicity in both pancreatic cancer cells and their 5FUR counterparts by modulating ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02671890

NCT02671890 | Disulfiram and Chemotherapy in Treating ... It is not yet known whether giving chemotherapy with or without disulfiram is a better treatment for refractory solid tumors or metastatic pancreatic cancer.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20192065

A Study of Disulfiram and Chemotherapy in Pancreas ... Disulfiram is a potential inhibitor of muscle degradation and may reduce tumor induced muscle wasting. Disulfiram may also help gemcitabine hydrochloride work ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8146747/

Overview of Antabuse® (Disulfiram) in Radiation and ... Antabuse, generic name disulfiram (DSF), is one of these drugs. Disulfiram has been approved to treat alcoholism for more than sixty years, only ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4391770/

A Phase IIb Trial Assessing the Addition of Disulfiram to ... The addition of disulfiram to a combination regimen of cisplatin and vinorelbine was well tolerated and appeared to prolong survival in patients with newly ...

8. journals.lww.com journals.lww.com/cmj/fulltext/2024/06200/disulfiram__a_novel_repurposed_drug_for_cancer.2.aspx

Disulfiram: A novel repurposed drug for cancer therapy Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug.