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

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to determine the safety and tolerability of combining sequential therapy of Irreversible Electroporation (IRE) and Immunotherapy (IO) for patients with locally advanced unresectable pancreas cancer following first-line treatment with chemotherapy and ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART).

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 data supports the effectiveness of this treatment for pancreatic cancer?

Research suggests that irreversible electroporation (a method using electric fields to destroy cancer cells) may improve survival and pain control in patients with locally advanced pancreatic cancer. Combining this with immunotherapy could help overcome resistance to other treatments, showing promise in early studies. ^{1 2 3 4 5}

Is the combination of electroporation and immunotherapy safe for humans?

Pembrolizumab (Keytruda), used in immunotherapy, has been approved for various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, and more serious immune-related issues like pneumonitis (lung inflammation) and thyroid problems. These side effects occur in a small percentage of patients and are usually outweighed by the benefits in treating life-threatening conditions. ^{6 7 8 9 10}

How does the Electroporation + Immunotherapy treatment for pancreatic cancer differ from other treatments?

This treatment combines irreversible electroporation (a technique using electric fields to destroy cancer cells) with immunotherapy (which helps the immune system fight cancer), offering a novel approach that may overcome resistance to traditional therapies and minimize damage to surrounding tissues. ^{1 3 4 11 12}

Research Team

Mokenge Malafa, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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 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, 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]

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]

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]

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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. Greece pubmed.ncbi.nlm.nih.gov

Electroporation enhances therapeutic efficacy of anticancer drugs: treatment of human pancreatic tumor in animal model. [2013]

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

Irreversible electroporation for the management of pancreatic cancer: Current data and future directions. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Antitumor Effect and Immune Response of Nanosecond Pulsed Electric Fields in Pancreatic Cancer. [2022]

12. 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]