FOLFIRINOX + Digoxin for Pancreatic Cancer

Overseen By Erin E Rogers, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must not be taking: Intravenous antibiotics

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with resectable pancreatic cancer who have not previously received chemotherapy for this condition. It combines a standard chemotherapy regimen called FOLFIRINOX (which includes drugs such as 5-Fluorouracil, Irinotecan, and Oxaliplatin) with digoxin, a drug that may enhance oxygen flow in cancer cells. The trial seeks to determine if this combination is safe and manageable before and after surgery. Individuals with pancreatic cancer that can be surgically removed, without metastasis, might be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a condition that is a contra-indication to digoxin therapy, such as certain heart issues, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of FOLFIRINOX and digoxin is under study for safety and effectiveness in treating pancreatic cancer. FOLFIRINOX, a mix of folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin, has been used in various ways for pancreatic cancer. Past studies have demonstrated some safety, though patients have experienced side effects like low blood counts and tiredness.

Digoxin, typically used for heart conditions, is being tested in this study to help fight cancer by affecting how cells use oxygen. Its safety for heart issues is well-known due to its long history of use, but its role in cancer treatment remains under exploration.

This trial is in a middle phase, indicating that earlier tests in different settings found the treatment generally safe, but more information is needed to confirm this for pancreatic cancer. Participants might experience side effects, so staying informed and discussing any concerns with the study team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of FOLFIRINOX and digoxin for pancreatic cancer because it introduces a new approach to treatment. While the standard of care for pancreatic cancer often involves chemotherapy regimens like FOLFIRINOX alone, this study adds digoxin, typically used for heart conditions, to potentially enhance treatment effectiveness. Digoxin may help to improve the cancer-fighting effects of chemotherapy by making cancer cells more sensitive to treatment. This novel combination could provide a more powerful attack on the cancer, offering hope for improved outcomes in patients with resectable pancreatic cancer.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that FOLFIRINOX, a combination of chemotherapy drugs, effectively treats pancreatic cancer. Studies have found that it extends patients' lives and improves their quality of life compared to treatments like gemcitabine. In some research, FOLFIRINOX effectively targeted certain cancer cells. In this trial, participants will receive FOLFIRINOX along with digoxin, a medication for heart conditions, which might enhance the treatment by affecting a process that helps cancer survive in low-oxygen areas. While FOLFIRINOX has shown promise in past studies, researchers continue to investigate its effectiveness with digoxin for treating surgically removable pancreatic cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Jean Grem, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults (19+) with resectable pancreatic cancer, no distant metastasis, and good performance status. They must have normal organ function, not received prior treatment for pancreatic cancer, and be disease-free from other cancers for 5+ years. Pregnant women or those with certain health conditions like heart failure or active infections cannot participate.

Inclusion Criteria

I understand my disease is cancerous and I have given written consent.

Your blood levels of potassium, magnesium, and calcium are within the normal range.

I have not had chemotherapy for pancreatic cancer.

Exclusion Criteria

I cannot have a laparoscopy due to many past abdominal surgeries.

I cannot take digoxin due to health reasons.

I do not have any serious ongoing illnesses like heart failure or uncontrolled infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive FOLFIRINOX chemotherapy and digoxin for 4-5 months prior to surgery

16-20 weeks

IV chemotherapy at 2-week intervals, re-staging imaging after 4 doses

Surgical Exploration

Participants undergo surgical exploration approximately 4 weeks after the last dose of chemotherapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with measurement of circulating cell free tumor DNA at 3-month intervals

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• 5Fluorouracil
• Digoxin
• Irinotecan
• Oxaliplatin

Trial Overview The study tests the safety and effectiveness of adding digoxin to FOLFIRINOX chemotherapy in treating resectable pancreatic cancer. Digoxin is being investigated for its potential to affect the hypoxia pathway which might improve treatment outcomes.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 5 Interventions

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.

5Fluorouracil is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in Canada as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in United States as Adrucil for:

• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Approved in European Union as Fluorouracil for:

• Actinic keratosis
• Basal cell carcinoma
• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Jean Grem, MD

Lead Sponsor

Trials

1

Recruited

10+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a multicenter phase II study involving 31 chemotherapy-naïve Japanese patients with advanced pancreatic cancer, the modified FOLFIRINOX (mFX) regimen showed a response rate of 38.7% and a median overall survival of 14.9 months, indicating its efficacy as a first-line treatment.

While mFX resulted in fewer Grade 3 or 4 non-hematological adverse events compared to the standard FOLFIRINOX regimen, it still had a high incidence of hematological adverse events, particularly neutropenia (83.9%), suggesting the need for further optimization to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. Yoshida, K., Iwashita, T., Uemura, S., et al.[2022]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

In a study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).

Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

In a study of 289 patients with advanced pancreatic ductal adenocarcinoma, the FOLFOXIRI chemotherapy regimen showed similar overall survival (11.1 months) compared to the standard FOLFIRINOX regimen (11.6 months), indicating no significant therapeutic advantage for FOLFOXIRI.

FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events (28.7% vs. 19.5% for FOLFIRINOX), suggesting that while it is feasible, it may lead to more severe side effects without improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. Vienot, A., Chevalier, H., Bolognini, C., et al.[2020]

Modified FOLFIRINOX, which eliminates bolus 5-FU, shows an improved safety profile with low rates of severe side effects, such as only 3% experiencing grade 4 neutropenia, while maintaining efficacy in treating pancreatic cancer.

In patients with nonmetastatic pancreatic cancer, modified FOLFIRINOX resulted in a median overall survival of 17.8 months and a median progression-free survival of 13.7 months, indicating promising activity in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Mahaseth, H., Brutcher, E., Kauh, J., et al.[2022]

In a study of 1835 patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with (m)FOLFIRINOX, the median overall survival was 18.7 months for locally advanced cases, 23.2 months for borderline resectable cases, and 31.2 months for potentially resectable cases, indicating varying outcomes based on disease stage.

The study also found that 37.9% of patients underwent surgical resection, with a median overall survival of 38.3 months for those who had surgery, highlighting the importance of resectability in improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. Janssen, QP., van Dam, JL., Doppenberg, D., et al.[2023]

In a study of 19 patient-derived pancreatic cancer cell lines, FOLFIRINOX showed optimal sensitivity in six cell lines, while three cell lines responded better to gemcitabine plus nab-paclitaxel (Gem-Pac), indicating that different regimens may work better for different patients.

The findings suggest that understanding the specific sensitivity of cancer cells to these treatments could help identify biomarkers, which may guide personalized chemotherapy choices for patients with pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. Begg, SKS., Birnbaum, DJ., Clark, JW., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04141995

Study Details | NCT04141995 | FOLFIRINOX With Digoxin ... 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 ...

2. withpower.com withpower.com/trial/folfirinox-digoxin-for-pancreatic-cancer-20ab6

FOLFIRINOX + Digoxin for Pancreatic Cancer In a study of 19 patient-derived pancreatic cancer cell lines, FOLFIRINOX showed optimal sensitivity in six cell lines, while three cell lines responded better ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38319559/

Real Life Data and Outcome of FOLFIRINOX Use in ... Results: The results showed a median overall survival of 228 days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11208991/

Clinical outcome of patients with inoperable pancreatic ... The data indicated that patients receiving GnP as first-line therapy were less likely to switch to FOLFIRINOX and, consequently, had a worse prognosis.

5. eviq.org.au eviq.org.au/medical-oncology/upper-gastrointestinal/pancreas-and-biliary/1512-pancreas-metastatic-folfirinox-modified-fl

Pancreas metastatic FOLFIRINOX (modified) (fluorouracil ... CONCLUSION: FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28062950/

Efficacy and Safety of FOLFIRINOX in Locally Advanced ... The aim of the study was to prospectively collect and analyse data on efficacy and safety of a modified FOLFIRINOX regimen in LAPC patients ...