Clinical Trials /

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

NCT03714555

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Disulfiram-Copper Gluconate in Met Pancreas Cancer w Rising CA19-9 on Abraxane-Gemzar, FOLFIRINOX or Gemcitabine
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CAN-203
  • NCT ID: NCT03714555

Conditions

  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper GluconateNab-Paclitaxel/Gemcitabine + DSF/Cu
FOLFIRINOX regimen Plus Disulfiram/Copper GluconateNab-Paclitaxel/Gemcitabine + DSF/Cu
Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper GluconateNab-Paclitaxel/Gemcitabine + DSF/Cu

Purpose

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.

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 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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Nab-Paclitaxel/Gemcitabine + DSF/CuActive ComparatorSubjects 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.
  • nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
  • FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
  • Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
FOLFIRINOX +DSF/CuActive ComparatorSubjects 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.
  • nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
  • FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
  • Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Single-Agent Gemcitabine +DSF/CuActive ComparatorSubjects 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.
  • nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
  • FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
  • Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate

Eligibility Criteria

        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:

               -  AST (SGOT), 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.
      
Maximum Eligible Age:105 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Change in plasma CA19-9 level (at least 30%) from baseline

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Complete response rate as defined by CT scan using RECIST 1.1 criteria
Measure: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
Safety Issue:
Description:Partial response as defined by CT scan using RECIST 1.1 criteria
Measure: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
Safety Issue:
Description:Complete response as defined by CT scan using RECIST 1.1 criteria
Measure: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
Safety Issue:
Description:Overall response rate as defined by CT scan using RECIST 1.1 criteria
Measure:Overall Survival
Time Frame:From date of enrollment until date of death assessed up to 100 months
Safety Issue:
Description:The length of time from the start of treatment that patients are still alive
Measure: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
Safety Issue:
Description:Change in serum albumin level as a result of treatment
Measure: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
Safety Issue:
Description:Change in body weight as a result of treatment
Measure: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
Safety Issue:
Description:Change in muscle area at the L3 level using CT scan. Only is L3 is visualized with normally scheduled standard of care CT Scan
Measure:Incidence of Toxicities
Time Frame:From date of enrollment until the date of follow-up, 30 days after last treatment
Safety Issue:
Description:Physical exam and laboratory testing will be completed and toxicity grading assessed and documented using CTCAE version 4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:HonorHealth Research Institute

Last Updated

December 6, 2019