Pancreas CancerPhase 2NCT04141995
FOLFIRINOX With Digoxin in Patients With Resectable Pancreatic Cancer
A Phase 2 study testing Digoxin, 5Fluorouracil and Calcium Leucovorin in people with Pancreas Cancer and Adenocarcinoma of the Pancreas, run by University of Nebraska at 1 site in United States.
Trial summary
The purpose of this study is to determine the feasibility and safety of combining digoxin as a modulator of the hypoxia pathway in combination with FOLinic acid, 5-Fluorouracil, IRINotecan and OXaliplatin (FOLFIRINOX) in participants with resectable pancreatic cancer. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Pancreas Cancer, Adenocarcinoma of the Pancreas
- What is being tested?
- Digoxin, 5Fluorouracil and Calcium Leucovorin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2021to 13 May 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed pancreatic adenocarcinoma. Participants must have resectable disease with no evidence of distant metastasis.
- 19 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) of 0-1 (fully active to restricted in strenuous activity).
- Chemotherapy for malignancies other than pancreatic cancer completed > 5 years ago and is no evidence of the prior malignancy at time of study entry.
- Radiographically assessable disease.
- Initial absolute neutrophil count (ANC) greater than or equal to 1000/μL and platelet count greater than or equal to 100,000/μL.
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- Normal serum potassium, magnesium and corrected calcium level.
- Serum creatinine less than or equal to 2.0 mg/dL.
- Total bilirubin <= 1.5 mg/dL [unless the participant has Gilbert disease with elevated non-conjugated (indirect) bilirubin; in such cases, the indirect bilirubin should be <= 1.0 mg/dL].
- If participant has biliary obstruction, biliary decompression will be required. Either endoscopic placement of biliary stent or percutaneous transhepatic drainage are acceptable. Once biliary drainage has been established, institution of FOLFOX therapy may proceed when the total bilirubin falls to <= 5.0 mg/dL. The addition of irinotecan will be delayed until the total bilirubin is 1.5 mg/dL or lower.
- Awareness of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.
- No prior chemotherapy for pancreatic cancer.
Who cannot join
- Unable to undergo staging laparoscopy, such as a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or might be potentially harmful.
- A contra-indication to receiving digoxin therapy (e.g., AV block, sick sinus syndrome, bradycardia, hypersensitivity to digoxin or digitalis preparations).
- Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the participant to receive the therapy in this study with reasonable safety.
- Pregnant and nursing women (risk posed by chemotherapy agents). Female participants of childbearing potential must have a negative urine pregnancy test before receiving the first dose of study drug.
- Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, adequately treated non-invasive carcinomas, or other cancers from which the participant has been disease-free least 5 years.
- Known HIV infection or active hepatitis B or C infection (concern for increased toxicity).
- Active autoimmune disease [e.g., rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis (AS)].
- Recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficienciess, hypogammaglobulinemia, or dysgammaglobulinemia.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: A Phase IIa (Pilot) Study of Neoadjuvant Chemotherapy With Folinic Acid, 5-FU, Irinotecan and Oxaliplatin (FOLFIRINOX) With Digoxin in Patients With Resectable Pancreatic Cancer
The purpose of this study is to determine the feasibility and safety of combining digoxin as a modulator of the hypoxia pathway in combination with FOLinic acid, 5-Fluorouracil, IRINotecan and OXaliplatin (FOLFIRINOX) in participants with resectable pancreatic cancer.
Read the detailed description
Participants with resectable pancreatic cancer will be treated with oxaliplatin 85 mg/m² IV over 2 hours, irinotecan 150 mg/m² given concurrently with folinic acid 400 mg/m² IV over 90 min, followed by a 46-hour infusion of 5-fluorouracil 2400 mg/m². Slow oral digitalization will be used starting with a daily dose of 0.125 (participants over age 65) or 0.25 mg (participants 65 or younger) per mouth daily. A steady-state will be achieved after five half-lives, which is about 7 to 10 days in the average participant. The initial blood level will be obtained one week after starting digoxin. Assuming the digoxin level is at steady-state and the renal function is stable, there is a linear relationship between digoxin dose and serum concentration. The target digoxin level is between 0.8 to 1.2 ng/mL. Participants will receive IV chemotherapy at 2 week intervals. Re-staging imaging will be performed after 4 doses. If the participants has stable or responsive disease, an additional 4 doses will be given followed by re-staging imaging. The participant will then undergo surgical exploration ~ 4 weeks after the last dose of chemotherapy.
The primary endpoint is clinical toxicity. Other endpoints are status of pathologic margins, response rate, pathologic stage, progression-free survival, and overall survival. The correlative endpoint is baseline exome sequencing of circulating cell free tumor DNA. Measurement of quantity of circulating cell free tumor DNA at 4 week intervals while on chemotherapy and prior to surgery; resume at 3 month intervals after surgery. Genomic DNA will be collected at baseline for pharmacogenetic studies of polymorphisms that may be pertinent for the drugs used in the study. Blood will be collected for analysis of possible biomarkers of response to digoxin modulation.
- Conditions
- Pancreas Cancer, Adenocarcinoma of the Pancreas
- Being tested
- Digoxin, 5Fluorouracil, Calcium Leucovorin, Irinotecan, Oxaliplatin
- Keywords
- Resectable
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Also called Lanoxin, Digitek, Digox
Tablet, Oral: Generic: 0.125 mg, 0.25 mg
5FluorouracilDrug
Also called Adrucil, 5-FU
5-FU will be given as a 46 hour continuous IV infusion
Calcium LeucovorinDrug
Also called Folinic Acid
IV injection over 90 minutes
IrinotecanDrug
Also called Camptothecin-11, CPT-11, Camptosar
IV administration over 90 minutes
OxaliplatinDrug
Also called Eloxatin
IV administration
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants start FOLFIRINOX. They will also begin digoxin and take it up to 4-5 months time period in patients with resectable pancreatic cancer. Digoxin is taken at the time of neo-adjuvant chemotherapy treatment, prior to surgery. After surgery, participants will continue with post-adjuvant chemotherapy. Receives: Drug: Digoxin; Drug: 5Fluorouracil; Drug: Calcium Leucovorin; Drug: Irinotecan; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Able to Undergo Resection Surgery
Regimen will be considered for further investigation if 14 of the 20 patients are able to undergo resection
Measured: 16 weeks
Secondary outcomes (1)
Number of Subjects With Grade 4 Thrombocytopenia and Grade 3-4 Diarrhea
Continuous monitoring will be performed to monitor toxicity using Pocock stopping boundary that yields the probability of crossing the boundary at most 0.05 when the toxicity rate is equal to 0.182 or 0.28 separately.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study start12 Feb 2021
- Primary completion13 May 2025
- Study completion13 May 2025
Why it stopped: Due to low accrual and futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pancreas CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jean Grem, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04141995
- Sponsor's protocol ID
- 0668-19-FB
- Other IDs
- 1P50CA127297-01A2
- Status last verified
- Apr 2025
- First submitted
- 18 Oct 2019
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa (Pilot) Study of Neoadjuvant Chemotherapy With Folinic Acid, 5-FU, Irinotecan and Oxaliplatin (FOLFIRINOX) With Digoxin in Patients With Resectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT04141995
- Acronym / sponsor ID
- 0668-19-FB
- Conditions
- Pancreas Cancer, Adenocarcinoma of the Pancreas
- Keywords
- Resectable
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to low accrual and futility
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 12 Feb 2021 (actual)
- Primary completion
- 13 May 2025 (actual)
- Study completion
- 13 May 2025 (actual)
- First posted
- 28 Oct 2019 (actual)
- Results
- Posted 21 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the feasibility and safety of combining digoxin as a modulator of the hypoxia pathway in combination with FOLinic acid, 5-Fluorouracil, IRINotecan and OXaliplatin (FOLFIRINOX) in participants with resectable pancreatic cancer.
Detailed description
Participants with resectable pancreatic cancer will be treated with oxaliplatin 85 mg/m² IV over 2 hours, irinotecan 150 mg/m² given concurrently with folinic acid 400 mg/m² IV over 90 min, followed by a 46-hour infusion of 5-fluorouracil 2400 mg/m². Slow oral digitalization will be used starting with a daily dose of 0.125 (participants over age 65) or 0.25 mg (participants 65 or younger) per mouth daily. A steady-state will be achieved after five half-lives, which is about 7 to 10 days in the average participant. The initial blood level will be obtained one week after starting digoxin. Assuming the digoxin level is at steady-state and the renal function is stable, there is a linear relationship between digoxin dose and serum concentration. The target digoxin level is between 0.8 to 1.2 ng/mL. Participants will receive IV chemotherapy at 2 week intervals. Re-staging imaging will be performed after 4 doses. If the participants has stable or responsive disease, an additional 4 doses will be given followed by re-staging imaging. The participant will then undergo surgical exploration ~ 4 weeks after the last dose of chemotherapy.
The primary endpoint is clinical toxicity. Other endpoints are status of pathologic margins, response rate, pathologic stage, progression-free survival, and overall survival. The correlative endpoint is baseline exome sequencing of circulating cell free tumor DNA. Measurement of quantity of circulating cell free tumor DNA at 4 week intervals while on chemotherapy and prior to surgery; resume at 3 month intervals after surgery. Genomic DNA will be collected at baseline for pharmacogenetic studies of polymorphisms that may be pertinent for the drugs used in the study. Blood will be collected for analysis of possible biomarkers of response to digoxin modulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Digoxin, Drug: 5Fluorouracil, Drug: Calcium Leucovorin, Drug: Irinotecan, Drug: OxaliplatinParticipants start FOLFIRINOX. They will also begin digoxin and take it up to 4-5 months time period in patients with resectable pancreatic cancer. Digoxin is taken at the time of neo-adjuvant chemotherapy treatment, prior to surgery. After surgery, participants will continue with post-adjuvant chemotherapy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Pathologically confirmed pancreatic adenocarcinoma. Participants must have resectable disease with no evidence of distant metastasis.
- 19 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) of 0-1 (fully active to restricted in strenuous activity).
- Chemotherapy for malignancies other than pancreatic cancer completed > 5 years ago and is no evidence of the prior malignancy at time of study entry.
- Radiographically assessable disease.
Key exclusion criteria (8 listed)
- Unable to undergo staging laparoscopy, such as a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or might be potentially harmful.
- A contra-indication to receiving digoxin therapy (e.g., AV block, sick sinus syndrome, bradycardia, hypersensitivity to digoxin or digitalis preparations).
- Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the participant to receive the therapy in this study with reasonable safety.
- Pregnant and nursing women (risk posed by chemotherapy agents). Female participants of childbearing potential must have a negative urine pregnancy test before receiving the first dose of study drug.
- Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, adequately treated non-invasive carcinomas, or other cancers from which the participant has been disease-free least 5 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DigoxinAlso: Lanoxin, Digitek, DigoxTablet, Oral: Generic: 0.125 mg, 0.25 mg | Drug | Treatment |
| 5FluorouracilAlso: Adrucil, 5-FU5-FU will be given as a 46 hour continuous IV infusion | Drug | Treatment |
| Calcium LeucovorinAlso: Folinic AcidIV injection over 90 minutes | Drug | Treatment |
| IrinotecanAlso: Camptothecin-11, CPT-11, CamptosarIV administration over 90 minutes | Drug | Treatment |
| OxaliplatinAlso: EloxatinIV administration | Drug | Treatment |
Primary outcome
Number of Patients Able to Undergo Resection Surgery
Time frame: 16 weeks
Regimen will be considered for further investigation if 14 of the 20 patients are able to undergo resection
1 secondary outcome
Number of Subjects With Grade 4 Thrombocytopenia and Grade 3-4 Diarrhea
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Grem, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Digoxin, 5Fluorouracil and Calcium Leucovorin in people with Pancreas Cancer and Adenocarcinoma of the Pancreas, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Able to Undergo Resection Surgery (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.