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

H

HonorHealth Research Institute

Status and phase

Terminated
Phase 2

Conditions

Metastatic Pancreatic Cancer

Treatments

Other: Concomitant Medication Review
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Other: Physical Exam
Other: AE Assessment
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
Diagnostic Test: Tumor Imaging
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
Diagnostic Test: Safety Laboratories

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT03714555
CAN-203

Details and patient eligibility

About

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.

Full 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.

Enrollment

1 patient

Sex

All

Ages

18 to 105 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

1 participants in 3 patient groups

Nab-Paclitaxel/Gemcitabine + DSF/Cu
Active Comparator group
Description:
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.
Treatment:
Diagnostic Test: Safety Laboratories
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Other: Physical Exam
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
Other: Concomitant Medication Review
Other: AE Assessment
Diagnostic Test: Tumor Imaging
FOLFIRINOX +DSF/Cu
Active Comparator group
Description:
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.
Treatment:
Diagnostic Test: Safety Laboratories
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Other: Physical Exam
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
Other: Concomitant Medication Review
Other: AE Assessment
Diagnostic Test: Tumor Imaging
Single-Agent Gemcitabine +DSF/Cu
Active Comparator group
Description:
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.
Treatment:
Diagnostic Test: Safety Laboratories
Drug: FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate
Drug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate
Other: Physical Exam
Drug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate
Other: Concomitant Medication Review
Other: AE Assessment
Diagnostic Test: Tumor Imaging

Trial documents
2

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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