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

11 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug FOLFIRINOX + Digoxin for Pancreatic Cancer?

Research shows that FOLFIRINOX, which includes 5-fluorouracil, irinotecan, and oxaliplatin, is a common first-line treatment for pancreatic cancer, although its effectiveness compared to other treatments like gemcitabine is not clearly superior. However, there is no specific data on the combination of FOLFIRINOX with Digoxin for pancreatic cancer. ^{1 2 3 4 5}

Is the FOLFIRINOX treatment generally safe for humans?

FOLFIRINOX, a combination of 5-fluorouracil, irinotecan, and oxaliplatin, is used for treating pancreatic cancer but is known to have a high rate of side effects, including blood-related issues like febrile neutropenia (fever with low white blood cell count). Modified versions of FOLFIRINOX have been developed to reduce these side effects while maintaining effectiveness. ^{1 5 6 7 8}

What makes the FOLFIRINOX + Digoxin treatment unique for pancreatic cancer?

The FOLFIRINOX + Digoxin treatment is unique because it combines a standard chemotherapy regimen (FOLFIRINOX) with Digoxin, a drug traditionally used for heart conditions, potentially offering a novel approach to enhance treatment effectiveness for pancreatic cancer. ^{1 2 4 9 10}

What is the purpose of this trial?

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.

Research Team

Jean Grem, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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 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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]

5. Turkey pubmed.ncbi.nlm.nih.gov

Folfirinox versus gemcitabine-cisplatin combination as first-line therapy in treatment of pancreaticobiliary cancer [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

10. China pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. [2020]