Disulfiram and Chemotherapy in Treating Patients With Refractory Solid Tumors or Metastatic Pancreatic Cancer

NCT02671890 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: MC1512R01CA195473NCI-2016-0000715-003194
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This partially randomized phase I trial studies the side effects and best dose of disulfiram when given together with chemotherapy in treating patients with a solid tumor that does not respond to treatment (refractory) or pancreatic cancer that has spread to other places in the body (metastatic) and to compare whether disulfiram and chemotherapy may reduce tumor induced muscle loss. Weight loss occurs in pancreatic cancer patients and is common in a multitude of other cancers. Patients with metastatic cancer and weight loss sometimes are not able to receive treatment due to physical weakness or debility. Disulfiram is a potential inhibitor of muscle degradation and may reduce tumor induced muscle wasting. Disulfiram may also help chemotherapy work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving chemotherapy with or without disulfiram is a better treatment for refractory solid tumors or metastatic pancreatic cancer.

Conditions

Metastatic Pancreatic Adenocarcinoma; Refractory Malignant Solid Neoplasm; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) (Cohort I)

  MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  28 days

Secondary Outcomes (8)

• Adverse events profile (Cohort I and II)

  Up to 30 days post-treatment

• Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Cohorts I and II)

  Up to 30 days post-treatment

• Overall survival (OS) (Cohort I and II)

  From registration until death due to any cause, assessed up to 3 years

• Change in muscle area at the L3 level using a computed tomography (CT) scan (Cohort II)

  Baseline to day 28

• Response rate (Cohort II)

  At 1 month post-treatment

Other Outcomes (2)

• Change in muscle protein expression level of total and phosphorylated (phosph)-signal transducer and activator of transcription 3 (STAT3) via immunohistochemistry

  Baseline to up to 35 days

• Changes in muscle messenger ribonucleic acid (mRNA) levels via real-time polymerase chain reaction

  Baseline to up to 35 days

Study Arms (2)

Cohort I (gemcitabine hydrochloride and disulfiram)

EXPERIMENTAL

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.

Drug: Disulfiram; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis

Cohort II (chemotherapy and disulfiram)

EXPERIMENTAL

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

Drug: Chemotherapy; Drug: Disulfiram; Other: Laboratory Biomarker Analysis

Interventions

Chemotherapy DRUG

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Cohort II (chemotherapy and disulfiram)

Disulfiram DRUG

Given PO

Also known as: Antabuse, DS, Tetraethylthioperoxydicarbonic Diamide, Teturamin, TTD

Cohort I (gemcitabine hydrochloride and disulfiram); Cohort II (chemotherapy and disulfiram)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Cohort I (gemcitabine hydrochloride and disulfiram)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort I (gemcitabine hydrochloride and disulfiram); Cohort II (chemotherapy and disulfiram)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 (dose escalation): histologic or cytologic proof of any solid tumor that is incurable with no standard therapy that is likely to make a major impact on clinical outcomes
• Cohort 2 (MTD) only: metastatic adenocarcinoma of the pancreas; prior systemic treatment for metastatic disease is allowed
• Cohort 2 (MTD) only: Patient is thought to be a short- or long-term candidate for chemotherapy in the opinion of the treating oncologist
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 7 days prior to registration)
• Platelet \>= 100,000/ mm\^3 (obtained =\< 7 days prior to registration)
• Total bilirubin =\< 2 x upper limit of normal (ULN) (obtained =\< 7 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x ULN (obtained =\< 7 days prior to registration)
• Creatinine =\< 1.5 x ULN (obtained =\< 7 days prior to registration)
• Hemoglobin \>= 9.0 g/dL (obtained =\< 7 days prior to registration)
• Cohort 2 (MTD) only: prothrombin time (PT)/international normalized ratio (INR) =\< 1.5 x ULN (only if muscle biopsy has not been waived, does not apply to non-Mayo sites that will not be conducting biopsies) (obtained =\< 7 days prior to registration)
• Ability to provide written informed consent
• Life expectancy \>= 12 weeks
• Cohort 2 (MTD) only: patient willing to undergo muscle biopsies at baseline and after 28 to 35 days of disulfiram/chemotherapy as required by the protocol unless the muscle biopsy has been waived after discussion with the principal investigator (PI); muscle biopsies will not be required at non-Mayo Clinic sites
• Cohort 2 (MTD) only: patient willing to have paraffin-embedded slides of the primary pancreas tumor or metastatic site, if available, sent to Mayo investigators for this study
• For women of childbearing potential only: negative urine or serum pregnancy test done =\< 7 days prior to registration

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, including localized infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• Untreated brain metastases
• Any of the following:
• Pregnant women
• Nursing women This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Baseline of grade 2 or worse peripheral sensory neuropathy
• Receiving phenytoin
• Unable to abstain from alcohol for the duration of the study

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Sanford Thief River Falls Medical Center

Thief River Falls, Minnesota, 56701, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Drug Therapy; Disulfiram; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Aminah Jatoi, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2016
• First Posted: February 2, 2016
• Study Start: February 25, 2016
• Primary Completion: May 8, 2024
• Study Completion: November 11, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Locations

US (2)