Chemotherapy + IRE for Pancreatic Cancer

Overseen By Robert Martin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Louisville

Disqualifiers: Pregnancy, Pacemaker, Metal implants, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with locally advanced pancreatic cancer. Researchers aim to determine the effectiveness of irreversible electroporation (IRE), a procedure using electrical pulses to destroy cancer cells, when combined with either FOLFIRINOX or gemcitabine, two common chemotherapy drugs. The goal is to identify which combination is more effective and easier for patients to tolerate. Individuals diagnosed with stage III pancreatic cancer and having a measurable tumor might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Previous studies have tested both FOLFIRINOX and gemcitabine for safety in treating pancreatic cancer. FOLFIRINOX has helped patients live longer than gemcitabine but causes more side effects, such as tiredness and low blood cell counts. Gemcitabine is less intense but can still cause side effects like nausea and fever.

Research on irreversible electroporation (IRE), a treatment that directly targets cancer cells, suggests it is generally safe. The risk of serious side effects, such as damage to nearby organs, has decreased over time. Each treatment has been studied for safety, but they have different side effect profiles. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy and irreversible electroporation (IRE) for pancreatic cancer because it offers a new way to tackle the disease. Unlike standard treatments that rely solely on chemotherapy drugs like FOLFIRINOX or Gemcitabine, IRE uses electrical pulses to create tiny holes in cancer cell membranes, which can enhance the effectiveness of chemotherapy. This innovative approach may improve drug delivery directly into the tumor, potentially leading to better outcomes and fewer side effects. By integrating IRE with chemotherapy, this treatment has the potential to improve the precision and impact of cancer therapy in ways that current options cannot.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that FOLFIRINOX, a combination of chemotherapy drugs, can extend the lives of people with pancreatic cancer. In studies, patients receiving FOLFIRINOX lived an average of 11.1 months, significantly longer than the 6.8 months for those treated with gemcitabine alone. Gemcitabine, another chemotherapy drug for pancreatic cancer, is known for being gentler on the body and improving survival compared to older treatments.

In this trial, participants will receive Irreversible Electroporation (IRE) combined with either FOLFIRINOX or Gemcitabine, depending on their prior chemotherapy regimen. IRE, a newer method, uses electrical pulses to destroy cancer cells by breaking their outer layer. Early research suggests that IRE can extend survival for some patients with locally advanced pancreatic cancer, with certain studies showing survival up to 30 months. Combining IRE with either chemotherapy method may enhance the treatment's effectiveness against pancreatic cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Robert Martin, MD, PhD

Principal Investigator

University of Louisville

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage III pancreatic cancer. Participants must have a measurable tumor, normal liver function (AST/ALT levels within three times the upper limit), and a stable post-surgery condition as confirmed by their surgeon. They should not be in another cancer treatment trial, pregnant or breastfeeding, have certain implants near the lesion, or recent heart attacks.

Inclusion Criteria

My condition is stage III pancreatic cancer.

My surgeon says my recovery after surgery is going as expected.

Your kidney function is better than a certain level.

Exclusion Criteria

I had a heart attack in the last 3 months.

I have metal implants near my cancer that cannot be removed.

You have a heart device that cannot be turned off during the procedure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either FOLFIRINOX or gemcitabine as peri-ablation treatment in combination with irreversible electroporation

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Triphase CT scans every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• FOLFIRINOX
• Gemcitabine
• Irreversible Electroporation (IRE)

Trial Overview The study compares two treatments for advanced pancreatic cancer: Irreversible Electroporation (IRE) combined with FOLFIRINOX versus IRE with gemcitabine. It aims to see which combination is more effective and tolerable for patients.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 3 Interventions

Irreversible electroporation and treatment with either FOLFIRINOX or Gemcitabine (based upon which chemotherapy regimen received prior to IRE)

FOLFIRINOX is already approved in European Union, United States for the following indications:

Approved in European Union as FOLFIRINOX for:

• Advanced pancreatic cancer

Approved in United States as FOLFIRINOX for:

• Metastatic pancreatic cancer

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Published Research Related to This Trial

In a study of 493 patients with resected pancreatic cancer, the modified FOLFIRINOX regimen resulted in significantly longer disease-free survival (21.6 months) and overall survival (54.4 months) compared to gemcitabine (12.8 months and 35.0 months, respectively).

While modified FOLFIRINOX showed better efficacy, it also had a higher incidence of severe adverse events (75.9% vs. 52.9% for gemcitabine), indicating a trade-off between effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. Conroy, T., Hammel, P., Hebbar, M., et al.[2023]

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 42 patients with locally advanced or metastatic biliary tract cancer treated with FOLFIRINOX, the regimen showed promising efficacy with a median overall survival of 15 months and a median time-to-progression of 8 months.

FOLFIRINOX was well-tolerated, with no severe toxicity reported, and resulted in a 29% partial response rate and a 14% rate of secondary macroscopically-complete resection, indicating its potential as a safe and effective first-line treatment for biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer. Ulusakarya, A., Karaboué, A., Ciacio, O., et al.[2021]

In a meta-analysis of 16 studies involving 3813 patients with metastatic pancreatic cancer, both GEM-NAB and FOLFIRINOX showed similar overall survival rates, despite FOLFIRINOX having a numerically longer median overall survival.

GEM-NAB was associated with lower rates of nausea and severe neutropenia compared to FOLFIRINOX, while FOLFIRINOX had lower rates of neurotoxicity and anemia, indicating that the choice between these treatments may depend on the patient's tolerance to side effects rather than a clear efficacy advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. Pusceddu, S., Ghidini, M., Torchio, M., et al.[2020]

FOLFIRINOX, a chemotherapy regimen combining 5-fluorouracil, irinotecan, and oxaliplatin, significantly improves overall survival (11.1 months) and progression-free survival (6.4 months) compared to gemcitabine (6.8 months and 3.3 months, respectively) in patients with metastatic pancreatic cancer, based on a trial with 342 participants.

While FOLFIRINOX is more effective and cost-effective than gemcitabine, it is associated with higher rates of severe side effects, such as neutropenia and diarrhea, necessitating careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. Kindler, HL.[2020]

Gemcitabine has been the standard treatment for advanced pancreatic cancer, showing improved survival compared to 5-fluorouracil, but combining it with other cytotoxic drugs has not significantly enhanced survival rates.

The introduction of the FOLFIRINOX regimen has significantly improved overall survival in advanced pancreatic cancer patients, with a median survival of 11.1 months compared to 6.8 months for gemcitabine alone, and nearly half of the patients in the FOLFIRINOX group were alive after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy of advanced pancreatic cancer: has the landscape changed? Choi, M., Razzaque, S., Kim, R.[2022]

In a study of 342 patients with metastatic pancreatic cancer, the FOLFIRINOX chemotherapy regimen significantly improved overall survival (11.1 months) compared to gemcitabine (6.8 months), indicating it is a more effective first-line treatment option.

While FOLFIRINOX showed a higher objective response rate (31.6% vs. 9.4% for gemcitabine), it also resulted in more adverse events, including a 5.4% incidence of febrile neutropenia, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Conroy, T., Desseigne, F., Ychou, M., et al.[2023]

The PRODIGE38-AMEBICA trial is a phase II/III study comparing modified FOLFIRINOX to CisGem in patients with advanced biliary tract cancer, aiming for a 73% rate of patients alive and without progression at 6 months for FOLFIRINOX, compared to 59% for CisGem.

The trial involves 188 patients and seeks to demonstrate an overall survival improvement of 4 months with modified FOLFIRINOX, highlighting its potential as a more effective treatment option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX versus CisGem first-line chemotherapy for locally advanced non resectable or metastatic biliary tract cancer (AMEBICA)-PRODIGE 38: Study protocol for a randomized controlled multicenter phase II/III study. Phelip, JM., Edeline, J., Blanc, JF., et al.[2022]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

In a comparison of two chemotherapy regimens for metastatic pancreatic cancer, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN), both treatments showed equivalent overall survival of 11.1 months and similar progression-free survival rates, indicating comparable efficacy.

However, the safety profiles differed: GN was associated with more frequent grade 3/4 anemia, while FFX led to higher rates of grade 3/4 vomiting and diarrhea, suggesting that while both treatments are effective, their side effects vary significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. Rapposelli, IG., Casadei-Gardini, A., Vivaldi, C., et al.[2022]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7081111/

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in ... Detailed outcomes data are summarized in Table 2. The objective response rate was 47.8% in the FOLFIRINOX group, compared to 37.1% in the ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2795978

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ... This randomized clinical trial examines 5-year outcomes and prognostic factors for overall survival for treatment with modified FOLFIRINOX ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... Results. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6320053/

Clinical outcomes of FOLFIRINOX in locally advanced ... About 1/3rd of patients with pancreatic cancers display unresectable localized disease, and the median overall survival (OS) is approximately 9 to 12 months for ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16393

Efficacy and safety of FOLFIRINOX versus gemcitabine- ... Results: FOLFIRINOX-treated patients (n = 3,020) demonstrated significantly longer overall survival (OS) than gemcitabine-treated patients (n = ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9087258/

Efficacy and safety of FOLFIRINOX as second-line ... This current meta-analysis analysed six studies that enrolled 858 patients to evaluate the effects and safety of FOLFIRINOX compared with FOLFIRI, FOLFOX and S ...