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

Phase 2

Terminated

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

• Registration Number: NCT03714555
• Lead Sponsor: HonorHealth Research Institute

Brief 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.

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 Timeline

• Study First Submitted: 2018-10-09
• Study First Submitted QC: 2018-10-18
• Study First Posted: 2018-10-22
• Study Start: 2019-10-17
• Primary Completion: 2020-07-22
• Study Completion: 2020-07-29
• Results First Submitted: 2023-08-24
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-26
• Last Update Submitted: 2023-09-26
• Results First Posted: 2023-10-18
• Last Update Posted: 2023-10-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single-Agent Gemcitabine +DSF/Cu	nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	Tumor Imaging	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	Concomitant Medication Review	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	Safety Laboratories	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.
FOLFIRINOX +DSF/Cu	FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate	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	Physical Exam	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate	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	Concomitant Medication Review	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	Safety Laboratories	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	AE Assessment	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.
Nab-Paclitaxel/Gemcitabine + DSF/Cu	Physical Exam	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	Tumor Imaging	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.
FOLFIRINOX +DSF/Cu	AE Assessment	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.
FOLFIRINOX +DSF/Cu	Physical Exam	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.
FOLFIRINOX +DSF/Cu	nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper Gluconate	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.
FOLFIRINOX +DSF/Cu	Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate	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	Safety Laboratories	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.
Single-Agent Gemcitabine +DSF/Cu	AE Assessment	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.
Single-Agent Gemcitabine +DSF/Cu	Concomitant Medication Review	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.
Single-Agent Gemcitabine +DSF/Cu	Tumor Imaging	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.
Single-Agent Gemcitabine +DSF/Cu	FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate	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.
Single-Agent Gemcitabine +DSF/Cu	Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate	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.

Primary Outcome Measures

Name	Time	Method
CA19-9 Plasma Level	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

Secondary Outcome Measures

Name	Time	Method
Stable Disease	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
Complete Tumor Response	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
Overall Response Rate	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
Partial Response	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
Overall Survival	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
Body Weight	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
Muscle Area at the L3 Level - Optional	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
Incidence of Toxicities	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
Serum Albumin	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

Trial Locations

Locations (1)

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States