Immunotherapy + Electroporation for Pancreatic Cancer

Overseen By Marilyn Donaldson, RN

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?

Compare the efficacy and tolerability of irreversible electroporation in combination with Nivolumab in patients with locally advanced pancreatic cancer.

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.

Is the combination of immunotherapy and electroporation safe for treating pancreatic cancer?

Research indicates that irreversible electroporation (a technique that destroys cancer cells without heat) is generally safe for treating pancreatic cancer, as it causes less damage to surrounding tissues like blood vessels and nerves. Combining this with immunotherapy (treatment that helps the immune system fight cancer) has been studied for safety, showing a promising safety profile in patients with advanced pancreatic cancer. ^{1 2 3 4 5}

How is the treatment of Immunotherapy + Electroporation for Pancreatic Cancer different from other treatments?

This treatment combines immunotherapy with irreversible electroporation, a non-thermal technique that destroys cancer cells while sparing surrounding tissues like blood vessels and nerves, which is particularly beneficial for pancreatic cancer where surgery is often not possible. ^{1 3 6 7 8}

What data supports the effectiveness of the treatment Immunotherapy + Electroporation for Pancreatic Cancer?

Research suggests that combining immunotherapy with irreversible electroporation (a technique that destroys cancer cells without heat) may help overcome resistance to traditional treatments in advanced pancreatic cancer. Studies indicate that irreversible electroporation can improve survival and pain control, showing promise as a treatment for this challenging condition. ^{1 2 3 6 7}

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]

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]

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]

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]

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]

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 (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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Stage III pancreatic cancer and the role of irreversible electroporation. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and feasibility of Irreversible Electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. [2022]

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

Percutaneous Approach to Irreversible Electroporation of the Pancreas: Miami Protocol. [2022]

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

A phase 1b trial of concurrent immunotherapy and irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. [2023]

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

Irreversible Electroporation for Locally Advanced Pancreatic Cancer: Where Do We Stand in 2017? [2018]

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

Preclinical evaluation of a novel single-shot pulsed field ablation system for pulmonary vein and atrial ablation. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Differential effect of high-frequency electroporation on myocardium vs. non-myocardial tissues. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Locally Recurrent Pancreatic Cancer After Surgical Resection. [2023]