Immunotherapy + Electroporation for Pancreatic Cancer

Overseen By Robert Martin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Louisville

Disqualifiers: Pregnancy, Breastfeeding, Cardiac pacemaker, 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: 6

Duration: Approximately 3 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment for individuals with locally advanced pancreatic cancer. It combines irreversible electroporation, a technique using electrical pulses to destroy cancer cells, with Nivolumab, an immunotherapy drug that helps the immune system fight cancer. Researchers aim to determine the effectiveness and tolerability of this combination in treating the disease. Individuals diagnosed with stage III pancreatic cancer and measurable tumors might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

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.

What prior data suggests that irreversible electroporation and Nivolumab are safe for pancreatic cancer patients?

Research has shown that irreversible electroporation (IRE) has been studied as a treatment for pancreatic cancer. In a study with 98 patients, including 29 with pancreatic cancer, IRE was generally safe, with no major safety issues reported.

Nivolumab, a type of immunotherapy, has also been tested in people with pancreatic cancer. Studies indicate it is generally safe, with side effects similar to other treatments for this cancer. Notably, nivolumab is already used for other types of cancer, which supports confidence in its safety.

Overall, both treatments have been manageable for patients, with no unexpected safety problems reported in previous studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about using irreversible electroporation combined with nivolumab for pancreatic cancer because it offers a novel approach compared to standard chemotherapy and radiation. Irreversible electroporation uses electrical pulses to create tiny holes in cancer cell membranes, effectively destroying them without harming surrounding tissue. Paired with nivolumab, an immunotherapy drug that boosts the immune system's ability to fight cancer, this combination has the potential to enhance treatment effectiveness and improve outcomes for patients. Unlike traditional treatments that often come with significant side effects, this method aims to target cancer cells more precisely, potentially leading to better tolerability and efficacy.

What evidence suggests that irreversible electroporation combined with Nivolumab could be effective for pancreatic cancer?

Studies have shown that irreversible electroporation (IRE) can effectively treat pancreatic cancer. In one study, IRE successfully destroyed 84.3% of target tumors within six weeks. Research also suggests that IRE may extend the lives of patients with locally advanced pancreatic cancer, though it requires careful management of side effects. In this trial, all patients will undergo IRE and receive nivolumab. Nivolumab has been found to improve overall survival in patients with advanced pancreatic cancer when combined with chemotherapy. In another study, patients receiving nivolumab had a one-year survival rate of 54.8%. Together, these treatments offer promising options for addressing difficult-to-treat pancreatic cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Robert C. Martin, MD,PhD,FACS

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 who can follow the study plan and have signed consent. They must have a measurable tumor and good kidney function. It's not for those in other cancer trials, pregnant or breastfeeding individuals, people with certain heart devices or metal implants near the tumor, or recent heart attack survivors.

Inclusion Criteria

My condition is stage III pancreatic cancer.

Willing and able to comply with the protocol requirements

Glomerular Filtration Rate > 60 m/L/min/1.73 m(2)

Exclusion Criteria

I had a heart attack in the last 3 months.

Have a cardiac pacemaker or Implantable Cardioverter Defibrillator implanted that cannot be deactivated during the procedure

Participating in another clinical trial for the treatment of cancer at the time of screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo irreversible electroporation and are treated with nivolumab post-operatively

Approximately 3 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Visits every 3 months for CT scans

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

4 years

CT scans every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Irreversible Electroporation
• Nivolumab

Trial Overview The study tests how well irreversible electroporation (a technique to destroy cancer cells using electricity) works alongside Nivolumab (an immunotherapy drug) in treating advanced pancreatic cancer. The goal is to see if this combination improves patient outcomes.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 2 Interventions

All patients undergoing irreversible electroporation will be treated with nivolumab

Irreversible Electroporation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as NanoKnife for:

• Soft tissue tumors
• Pancreatic cancer

Approved in United States as NanoKnife for:

• Soft tissue tumors
• Pancreatic cancer

Approved in Canada as NanoKnife for:

• Soft tissue tumors
• Pancreatic cancer

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Published Research Related to This Trial

Irreversible electroporation is a promising non-thermal ablative technique for treating locally advanced pancreatic cancer, which is often not suitable for conventional surgical resection.

Current evidence, primarily from non-randomized studies, suggests that this method may enhance overall survival and pain management for patients, but further randomized controlled trials are necessary to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stage III pancreatic cancer and the role of irreversible electroporation. Al Efishat, M., Wolfgang, CL., Weiss, MJ.[2022]

Pulsed-field ablation (PFA) using high-frequency irreversible electroporation (HF-IRE) demonstrated a tissue-specific effect, causing significant damage to cardiac muscle while sparing vascular and neural tissues, indicating its potential safety profile for non-cardiac applications.

In a study involving 23 rodents, higher voltage protocols (900 V) resulted in larger myocardial lesions compared to lower voltages, but no damage was observed in the carotid artery, suggesting that low-amplitude HF-IRE protocols may be safe for surrounding tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effect of high-frequency electroporation on myocardium vs. non-myocardial tissues. Moshkovits, Y., Grynberg, D., Heller, E., et al.[2023]

Irreversible electroporation is a promising nonthermal technique for treating locally advanced pancreatic adenocarcinoma, which is typically considered unresectable due to its involvement with critical blood vessels.

This method induces permanent cell death in cancer cells while minimizing damage to surrounding tissues, such as blood vessels and nerves, potentially improving treatment outcomes for patients with this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible Electroporation for Locally Advanced Pancreatic Cancer: Where Do We Stand in 2017? Tasu, JP., Vesselle, G., Herpe, G., et al.[2018]

Irreversible electroporation (IRE) is a feasible treatment for locally recurrent pancreatic cancer after surgical resection, but it carries significant risks, including severe complications in 20% of patients, with one patient dying as a result.

The median overall survival after IRE was 16.5 months, with two patients surviving over 42 months without signs of recurrence, indicating potential efficacy but highlighting the need for further research to identify suitable candidates for this high-risk procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Locally Recurrent Pancreatic Cancer After Surgical Resection. Månsson, C., Nilsson, A., Nygren, P., et al.[2023]

The NanoKnife Low Energy Direct Current (IRE) System was evaluated in a study of 10 patients with unresectable pancreatic cancer, showing a 10% rate of procedure-related complications, indicating it is a relatively safe treatment option.

Despite some early disease progression in a few patients, the overall survival rate was 7.5 months, suggesting that IRE may provide a new avenue for managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of Irreversible Electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. Paiella, S., Butturini, G., Frigerio, I., et al.[2022]

Pulsed field ablation (PFA) using a novel 8-French, 16-electrode catheter was shown to safely create large, durable lesions in atrial tissues of 23 swine, one canine, and one ovine, with no significant adverse effects on the phrenic nerve or esophagus.

The study demonstrated that PFA effectively reduced atrial electrogram amplitude and produced transmural lesions without thermal damage, with histological changes in the esophagus resolving within 21 days, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a novel single-shot pulsed field ablation system for pulmonary vein and atrial ablation. Aryana, A., Ji, SY., Hata, C., et al.[2023]

Irreversible electroporation is a promising nonthermal treatment option for patients with unresectable locally advanced pancreatic cancer, which has traditionally had poor outcomes.

The review emphasizes the importance of careful patient selection, preparation, and follow-up to ensure safe and effective tumor ablation using this technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Approach to Irreversible Electroporation of the Pancreas: Miami Protocol. Venkat, S., Hosein, PJ., Narayanan, G.[2022]

Irreversible electroporation (IRE) combined with nivolumab shows a promising safety profile, as no dose-limiting toxicities were observed in a phase 1b clinical trial involving 10 patients, with a median follow-up of 12 months.

The combination therapy resulted in a mean time to progression of 6.3 months and a median overall survival of 18.0 months, suggesting potential efficacy in treating locally advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b trial of concurrent immunotherapy and irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. O'Neill, C., Hayat, T., Hamm, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10002122/

Irreversible Electroporation in Pancreatic Cancer—An ... Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer.

2. anthem.com anthem.com/medpolicies/abc/active/mp_pw_c142348.html

SURG.00126 Irreversible Electroporation The primary efficacy endpoint, defined as the percentage of target tumors successfully eradicated by the 6-week follow-up, was 84.3% in the thermal ablation ...

3. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=40204

Irreversible Electroporation for Cancer (DL40205) Use this page to view details for the Local Coverage Determination for Irreversible Electroporation for Cancer.

4. aetna.com aetna.com/cpb/medical/data/800_899/0828.html

Irreversible Electroporation (NanoKnife) - Medical Clinical ... Scheffer et al (2014a) provided an overview of current clinical results of IRE, a novel, non-thermal tumor ablation technique that uses electric pulses to ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772632022000186

Is irreversible electroporation (IRE) an effective and safe ... IRE can benefit the survival of patients with locally advanced pancreatic cancer, but related adverse events should be treated with caution.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12376352/

Real-world safety of irreversible electroporation therapy for ... Among the 98 patients included in our study from 2014 to 2024, there were 29 cases of pancreatic cancer, 19 cases of liver cancer, 10 cases of ...