Electroporation + Immunotherapy for Pancreatic Cancer

Overseen By Alicia Chin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Enoxaparin

Must not be taking: Corticosteroids, Immunosuppressants, CYP3A4 inducers, others

Disqualifiers: Cardiovascular disease, Pacemakers, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced pancreatic cancer that cannot be surgically removed. It combines irreversible electroporation (IRE), a technique using electrical pulses to target cancer cells, with an immune-boosting drug called pembrolizumab. The trial aims to determine if this combination is safe and tolerable for patients. It is suitable for those who have already undergone chemotherapy and specialized radiation therapy without cancer progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on medications that prolong the QT interval or induce Torsades de Pointes, or if you are on strong inhibitors or inducers of CYP3A4 without switching to a different medication before starting the study.

What prior data suggests that this combination of irreversible electroporation and immunotherapy is safe for pancreatic cancer patients?

A previous study found that a treatment called Irreversible Electroporation (IRE) showed promise for treating pancreatic cancer. However, it carried a 17.6% risk of complications, such as irregular heartbeat and collapsed lung, which were generally manageable.

Research has shown that Pembrolizumab, a drug approved for melanoma, is being tested for pancreatic cancer. It has been used safely with other treatments in some studies and has shown early signs of fighting cancer. However, its safety specifically for pancreatic cancer remains unproven.

This trial is in its early stages, focusing on the safety of these treatments when used together. This step is crucial to determine if they work effectively without causing excessive problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of irreversible electroporation (IRE) and pembrolizumab for pancreatic cancer because it introduces a novel approach to treatment. IRE uses electrical pulses to create tiny pores in cancer cells, which can help destroy them without harming surrounding healthy tissue. This is different from traditional treatments like chemotherapy and radiation, which can impact both cancerous and healthy cells. Pembrolizumab, an immunotherapy drug, helps the immune system recognize and attack cancer cells more effectively. By combining these two methods, the treatment aims to enhance the body's natural defenses while minimizing damage to healthy tissues, offering new hope for those battling pancreatic cancer.

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

Research has shown that irreversible electroporation (IRE) can effectively kill cancer cells by disrupting their outer layer. In some studies, the survival rate of cancer cells dropped to just 10% with IRE. For pancreatic cancer, IRE has been linked to better overall survival when combined with chemotherapy. In this trial, participants will receive IRE using the NanoKnife system. Another treatment in this trial is pembrolizumab, a type of immunotherapy, which has also shown promise, with some patients living longer. While individual responses can vary, these treatments have produced encouraging results in combating difficult pancreatic cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Mokenge Malafa, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with locally advanced pancreatic cancer that can't be removed by surgery. They should have already undergone initial chemotherapy and a type of precise radiation therapy called A-SMART.

Inclusion Criteria

I have recovered from the side effects of my previous cancer treatment.

I am fully active or can carry out light work.

My pancreatic cancer is confirmed and is at stage 3.

Exclusion Criteria

Participant has other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate patient participation in the clinical study.

Participants who have implanted cardiac pacemakers, defibrillators, or implanted devices with bare metal parts in the thoracic cavity, abdomen, and/or retroperitoneum.

I am not on long-term steroids or immunosuppressants, and I don't have an active autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo irreversible electroporation (IRE) followed by a 200mg dose of pembrolizumab approximately 1 week later

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

4 visits (in-person)

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Irreversible Electroporation
• Pembrolizumab

Trial Overview The study tests the safety of using Irreversible Electroporation (IRE), a technique to destroy cancer cells, followed by Pembrolizumab, an immunotherapy drug, in treating pancreatic cancer.

How Is the Trial Designed?

Group I: IRE/Pembrolizumab Experimental Treatment 2 Interventions

Participants will undergo irreversible electroporation (IRE) using the NanoKnife system. About 1 week following IRE, study participants will receive a 200mg dose of pembrolizumab.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Angiodynamics, Inc.

Industry Sponsor

Trials

27

Recruited

3,100+

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

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 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]

Irreversible electroporation (IRE) is a new non-thermal treatment for inoperable pancreatic cancer that aims to reduce the risk of damage to surrounding tissues compared to traditional thermal ablation methods.

Initial clinical data suggest that IRE may be a safer and more effective option for managing pancreatic cancer, which currently has a poor prognosis and limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation for the management of pancreatic cancer: Current data and future directions. Spiliopoulos, S., Reppas, L., Filippiadis, D., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Electroporation therapy (EPT) combined with chemotherapeutic agents significantly enhances the treatment efficacy for pancreatic tumors, leading to notable tumor regression in a study involving nude mice over 89 days.

Among the tested drugs, bleomycin was the most effective, followed by mitomycin C and carboplatin, suggesting that EPT could be a promising approach for future clinical trials in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroporation enhances therapeutic efficacy of anticancer drugs: treatment of human pancreatic tumor in animal model. Nanda, GS., Sun, FX., Hofmann, GA., et al.[2013]

Nanosecond pulsed electric fields (nsPEFs) effectively inhibited tumor growth in pancreatic cancer models, leading to decreased tumor volumes and increased apoptosis in cancer cells, as confirmed by various staining techniques and imaging methods.

NsPEFs treatment significantly altered the tumor immune microenvironment by increasing CD8+ T lymphocytes and decreasing immune suppressive cells, which suggests that nsPEFs not only target tumors directly but also enhance the body's immune response against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Effect and Immune Response of Nanosecond Pulsed Electric Fields in Pancreatic Cancer. Zhao, J., Chen, S., Zhu, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11640091/

Initial Results from the DIRECT Registry Study - PMC Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis.

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

Irreversible Electroporation in Pancreatic Cancer—An ... M1 virus monotherapy reduced the survival of cancer cells to about 60%, and with the addition of electroporation, the survival rate was only 10% ...

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

SURG.00126 Irreversible Electroporation For well-selected patients, IRE can achieve encouraging survival outcomes”. However, a complication rate of 17.6% should not be overlooked. Entry into this ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S108925162030024X

Irreversible Electroporation for Locally Advanced ... IRE offers LAPC patients an efficacious treatment option when combined with chemotherapy. Several studies have confirmed overall survival benefit.

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

Proposed LCD - Irreversible Electroporation for Cancer Meta-analysis showed that IRE ablation is safe and effective for liver cancer treatment. Bile duct, intestine and blood vessels adjacent to the tumors are ...

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

Irreversible Electroporation (NanoKnife) - Medical Clinical ... As for the safety of IRE, there were only a few reported complications (cardiac arrhythmia, pneumothorax, and electrolyte disturbance) that were mostly ...