Disulfiram-Copper Gluconate in Met Pancreas Cancer w Rising CA19-9 on Abraxane-Gemzar, FOLFIRINOX or Gemcitabine

September 26, 2023 updated by: HonorHealth Research Institute

A Phase II Pilot Study of Disulfiram and Copper Gluconate in Patients With Metastatic Pancreatic Cancer and Rising CA-19-9 Levels While Receiving Abraxane-Gemcitabine or FOLFIRINOX or Single-Agent Gemcitabine

This is an open-label Phase 2 Pilot study to evaluate Disulfiram + Copper Gluconate in patients metastatic pancreatic cancer whose CA-19-9 levels rise while receiving nab-paclitaxel (Abraxane) plus gemcitabine (Gemzar) or FOLFIRINOX or single-agent gemcitabine (Gemzar). Patient must have received a minimum of 8 weeks of treatment and have rising CA-19-9 levels in the absence of radiographic evidence of progression.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study has 3 arms with 5 patients enrolled in each of the three arms. The three treatment arms are based upon whether the patient has previously received Abraxane-Gemcitabine or FOLFIRINOX or single-agent Gemcitabine without radiographic evidence of disease progression for a minimum of 8 weeks , based on the investigator's opinion, but with a rising Carbohydrate antigen 19-9 (CA 19-9) levels. Rising CA 19-9 is defined as an increased over baseline of > 20% in two consecutive time points within 8 days of each other. Study sites will provide all chemotherapy for patients participating in the study as a "standard of care". DSF/Cu (Disulfiram + Copper Gluconate) will be provided by the Sponsor and shipped from the Sponsor's central depot to the study sites. Sufficient amounts of DSF/Cu will be available at the study site prior to enrolling patients in the study.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85251
        • HonorHealth Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 101 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients must have histologically confirmed adenocarcinoma of the pancreas that is metastatic and for which potential curative measures, such as resection of an isolated metastasis, are not available. Patients with islet cell neoplasms are excluded.
  2. Patient should currently be receiving a chemotherapy regimen comprising FOLFIRINOX or Abraxane-Gemcitabine or single-agent Gemcitabine as front-line treatment for metastatic disease. Patients who have had chemotherapy in the adjuvant or neoadjuvant setting are eligible.
  3. Patients must have previously received a minimum of 8 weeks of therapy with Abraxane-Gemcitabine or FOLFIRINOX or single-agent Gemcitabine without radiographic evidence of disease progression based on the investigator's opinion, but a rising CA 19-9 level, and still be undergoing treatment with Abraxane-Gemcitabine or FOLFIRINOX or single-agent Gemcitabine. Increased CA 19-9 is defined as an increased over baseline of > 20% in two consecutive time points within 8 days of each other.
  4. Patient has one or more metastatic tumors measurable by CT scan. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
  5. Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 80 years of age.
  6. Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count ≥ 100,000/mm3 (100 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL.

  7. Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:

    • aspartate aminotransferase (AST) (SGOT), Alanine Transaminase (ALT) (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 × ULN is allowed. Total bilirubin ≤ 1.5 × ULN.
    • Serum creatinine < 1.5X ULN or estimated creatinine clearance of > 60 mL/min (per Cockroft-Gault formula)
  8. Patient has ECOG performance status from 0 to ≤ 1.
  9. Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

Exclusion Criteria:

  1. Patient has brain metastases.
  2. Patient has experienced an increase of ECOG to > 1 between Screening and enrollment.
  3. QTc > 480 msec if patient receiving oxaliplatin-containing regimen.
  4. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  5. Patient has a history of allergy or hypersensitivity to any of the study drugs, their pharmaceutical class or any of their excipients. The patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of Gemcitabine or Abraxane ® Prescribing Information package inserts or on the Investigator's Brochure for DSF/Cu.
  6. Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity.
  7. Patient is enrolled in any other clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of metastatic pancreatic cancer.
  8. Patient is unwilling or unable to comply with study procedures.
  9. Abraxane is metabolized by CYP2C8 and CYP3A4. Co-administration of substrates, inhibitors of CYP2C8 (see Appendix C) and/or CYP3A4 (see Appendix D) with Abraxane is not allowed. The following medications and substances are not allowed during the study: ritonavir, saquinavir, indinavir, nelfinavir, rifampicin, carbamazepine, phenytoin, efiravenz, or nerivapine, grapefruit (juice or seeds) or some herbals like St. John's wort.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nab-Paclitaxel/Gemcitabine + DSF/Cu
Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with Nab-Paclitaxel-Gemcitabine with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.
Other: Concomitant Medication Review
Prior and Concomitant Medication Review
Diagnostic test: Tumor Imaging
Tumor CT or MRI
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Diagnostic test: Safety Laboratories
Complete blood cell count (CBC) w Differential, comprehensive metabolic panel (CMP), Prothrombin time/international normalized ratio (PT/INR) Activated Partial Thromboplastin Time (aPTT), Urinalysis
Other: AE Assessment
Assessment of Adverse Events (AE)
Other: Physical Exam
Physical Exam, Weight, Vital Signs, Eastern Cooperative Oncology Group (ECOG) Performance Status
Active Comparator: FOLFIRINOX +DSF/Cu
Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with FOLFIRINOX and with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.
Other: Concomitant Medication Review
Prior and Concomitant Medication Review
Diagnostic test: Tumor Imaging
Tumor CT or MRI
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Diagnostic test: Safety Laboratories
Complete blood cell count (CBC) w Differential, comprehensive metabolic panel (CMP), Prothrombin time/international normalized ratio (PT/INR) Activated Partial Thromboplastin Time (aPTT), Urinalysis
Other: AE Assessment
Assessment of Adverse Events (AE)
Other: Physical Exam
Physical Exam, Weight, Vital Signs, Eastern Cooperative Oncology Group (ECOG) Performance Status
Active Comparator: Single-Agent Gemcitabine +DSF/Cu
Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with Single-Agent Gemcitabine and with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.
Other: Concomitant Medication Review
Prior and Concomitant Medication Review
Diagnostic test: Tumor Imaging
Tumor CT or MRI
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate dispensing
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Diagnostic test: Safety Laboratories
Complete blood cell count (CBC) w Differential, comprehensive metabolic panel (CMP), Prothrombin time/international normalized ratio (PT/INR) Activated Partial Thromboplastin Time (aPTT), Urinalysis
Other: AE Assessment
Assessment of Adverse Events (AE)
Other: Physical Exam
Physical Exam, Weight, Vital Signs, Eastern Cooperative Oncology Group (ECOG) Performance Status

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CA19-9 Plasma Level
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Change in plasma CA19-9 level (at least 30%) from baseline
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Tumor Response
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Complete response rate as defined by CT scan using RECIST 1.1 criteria
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Partial Response
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Partial response as defined by CT scan using RECIST 1.1 criteria
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Stable Disease
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Complete response as defined by CT scan using RECIST 1.1 criteria
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Response Rate
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall response rate as defined by CT scan using RECIST 1.1 criteria
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival
Time Frame: From date of enrollment until date of death assessed up to 100 months
The length of time from the start of treatment that patients are still alive
From date of enrollment until date of death assessed up to 100 months
Serum Albumin
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Change in serum albumin level as a result of treatment
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Body Weight
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Change in body weight as a result of treatment
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Muscle Area at the L3 Level - Optional
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Change in muscle area at the L3 level using CT scan. Only is L3 is visualized with normally scheduled standard of care CT Scan
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Incidence of Toxicities
Time Frame: From date of enrollment until the date of follow-up, 30 days after last treatment
Physical exam and laboratory testing will be completed and toxicity grading assessed and documented using CTCAE version 4.0
From date of enrollment until the date of follow-up, 30 days after last treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disulfiram/Copper Gluconate Serum Levels - Area Under the Curve (AUC)
Time Frame: Day 0 (pre-Cycle 1 Day 1) at pre-dose, 2 hours, 4 hours, 24 hours and 4 hours post-dose Cycle 1 Day 7
Optional Day 0 (pre-Cycle 1 Day 1) at pre-dose, 2 hours, 4 hours, 24 hours and 4 hours post-dose Cycle 1 Day 7
Day 0 (pre-Cycle 1 Day 1) at pre-dose, 2 hours, 4 hours, 24 hours and 4 hours post-dose Cycle 1 Day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

HonorHealth Research Institute

Collaborators

Cantex Pharmaceuticals

Investigators

  • Principal Investigator: Gayle Jameson, ACNP-BC, HonorHealth Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2019

Primary Completion (Actual)

July 22, 2020

Study Completion (Actual)

July 29, 2020

Study Registration Dates

First Submitted

October 9, 2018

First Submitted That Met QC Criteria

October 18, 2018

First Posted (Actual)

October 22, 2018

Study Record Updates

Last Update Posted (Actual)

October 18, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAN-203

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Pancreatic Cancer

Clinical Trials on Concomitant Medication Review

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe