Disulfiram-Copper Gluconate in Met Pancreas Cancer w Rising CA19-9 on Abraxane-Gemzar, FOLFIRINOX or Gemcitabine
Condition: Metastatic Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Safety Laboratories; AE Assessment; Physical Exam; Concomitant Medication Review; Tumor Imaging; 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
Intervention description: Complete blood cell count (CBC) w Differential, comprehensive metabolic panel (CMP), Prothrombin time/international normalized ratio (PT/INR) Activated Partial Thromboplastin Time (aPTT), Urinalysis; Assessment of Adverse Events (AE); Physical Exam, Weight, Vital Signs, Eastern Cooperative Oncology Group (ECOG) Performance Status; Prior and Concomitant Medication Review; Tumor CT or MRI; nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing; FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate dispensing; Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing
Intervention MeSH terms: Copper; Paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel; Folfirinox; Disulfiram
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 105 Years
Healthy volunteers: No

Summary:

      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.
    

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:

               -  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.