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.
Completed
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate | FOLFIRINOX +DSF/Cu | |
| FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate | FOLFIRINOX +DSF/Cu | |
| Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate | FOLFIRINOX +DSF/Cu |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Nab-Paclitaxel/Gemcitabine + DSF/Cu | Active Comparator | 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. |
|
| FOLFIRINOX +DSF/Cu | Active Comparator | 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. |
|
| Single-Agent Gemcitabine +DSF/Cu | Active Comparator | 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. |
|
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 |
| 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 |
| 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 |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | HonorHealth Research Institute |
July 16, 2021
