NanoKnife IRE for Pancreatic Cancer

(DIRECT Trial)

Not currently recruiting at 14 trial locations

Overseen By Elizabeth Manning

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Angiodynamics, Inc.

Must be taking: FOLFIRINOX

Disqualifiers: Pregnancy, Bleeding disorders, Epilepsy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for individuals with Stage 3 pancreatic cancer that cannot be surgically removed. It compares two groups: one receiving a chemotherapy regimen called modified FOLFIRINOX, and the other receiving the same chemotherapy plus a procedure called irreversible electroporation (IRE) using the NanoKnife System, which targets cancer cells with electrical pulses. The aim is to determine if adding NanoKnife IRE provides more benefit than chemotherapy alone. Suitable candidates for this trial have completed three months of modified FOLFIRINOX treatment without any signs of cancer progression. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you will need to be on the modified FOLFIRINOX chemotherapy regimen for at least 3 months as part of the trial.

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

Research has shown that using the NanoKnife System for irreversible electroporation (IRE) is generally safe, especially with heart monitoring. Early study results indicate that IRE can effectively target and destroy tumor cells while mostly sparing healthy tissue.

One study found that side effects from NanoKnife treatment have become less common. However, some patients have experienced digestive system injuries, which is important to consider.

The modified FOLFIRINOX chemotherapy has been used to treat pancreatic cancer and is known to cause side effects like nausea and fatigue.

Overall, both treatments appear promising, but they carry potential risks. Consulting with a healthcare provider is crucial to determine the best option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the NanoKnife IRE treatment for pancreatic cancer because it offers a unique approach compared to traditional options like surgery, chemotherapy, and radiation. Unlike these standard treatments, which can often damage surrounding healthy tissues, NanoKnife uses electrical pulses to precisely target and destroy cancer cells without harming the nearby healthy cells. This minimally invasive technique could potentially lead to fewer side effects and a quicker recovery for patients. Additionally, when combined with the modified FOLFIRINOX regimen, which is already known for its effectiveness in treating pancreatic cancer, there is hope for improved outcomes and survival rates.

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

Research has shown that the NanoKnife IRE (Irreversible Electroporation), tested in this trial, could aid in treating pancreatic cancer. Early studies found that IRE can significantly slow cancer cell growth. Specifically, patients with Stage 3 pancreatic cancer experienced a noticeable reduction in tumor spread with IRE. Initial safety data indicates that the procedure is generally well-tolerated. While more research is needed, these findings offer hope that NanoKnife IRE might become an effective part of pancreatic cancer treatment. Participants in this trial will receive either the NanoKnife IRE or the Modified FOLFIRINOX Regimen, which serves as the control treatment. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Stage 3 pancreatic cancer, as defined by NCCN guidelines, who have already undergone 3 months of modified FOLFIRINOX chemotherapy without disease progression. Participants must be in good physical health (ECOG status of 0 or 1 and ASA classification of 1 or 2) and agree to use effective birth control. Those with severe organ dysfunction, bleeding disorders, implanted electronic devices in the thoracic cavity, epilepsy, other neurological diseases, or kidney disease are excluded.

Inclusion Criteria

Your tumor is at an advanced stage according to the NCCN guidelines.

Provision of signed and dated informed consent form

The size of your tumor is no larger than 3.5cm after three months of treatment with a specific chemotherapy regimen.

Exclusion Criteria

Subjects who are or may be pregnant as determined by a positive pregnancy test or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 6 months after the last dose of chemotherapy

You can't handle being put to sleep with a strong muscle relaxant.

You are currently bleeding, taking blood thinners, or have low levels of hemoglobin, white blood cells, or platelets.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy with the modified FOLFIRINOX regimen for at least 3 months

12 weeks

Randomization

Participants are randomized to either the control arm or the IRE arm after completion of chemotherapy

1 week

IRE Treatment

Participants in the IRE arm receive irreversible electroporation with the NanoKnife System

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Modified FOLFIRINOX Regimen
• NanoKnife IRE

Trial Overview The study compares two groups: one receiving only the modified FOLFIRINOX chemotherapy regimen; the other getting this chemo followed by NanoKnife IRE treatment using an open or percutaneous approach. Patients are randomly assigned to either group after completing initial chemo and showing no signs of cancer progression. The follow-up period will last at least two years or until death.

How Is the Trial Designed?

Group I: IRE Experimental Treatment 2 Interventions

Group II: Control Active Control 1 Intervention

Who Is Running the Clinical Trial?

Angiodynamics, Inc.

Lead Sponsor

Trials

27

Recruited

3,100+

Published Research Related to This Trial

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 multicenter phase II study involving 31 patients with locally advanced pancreatic cancer (LAPC) and 44 with metastatic pancreatic cancer (MPC), modified FOLFIRINOX showed comparable efficacy to full-dose FOLFIRINOX in MPC, with a response rate of 35.1% and a median overall survival of 10.2 months.

The study found that modified FOLFIRINOX significantly reduced adverse events such as neutropenia, vomiting, and fatigue, while demonstrating notable efficacy in LAPC with a median progression-free survival of 17.8 months and overall survival of 26.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Stein, SM., James, ES., Deng, Y., et al.[2022]

In a study of 71 patients with advanced pancreatic cancer who progressed after initial treatment with modified FOLFIRINOX, second-line chemotherapy resulted in a 7.1% partial response rate and a 27.1% disease stabilization rate.

The median overall survival for these patients was 6.2 months, with CA19.9 levels above the normal limit indicating worse survival outcomes, suggesting that certain prognostic factors can help identify patients who may benefit more from salvage chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. Caparello, C., Vivaldi, C., Fornaro, L., et al.[2022]

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]

In a study of 69 chemotherapy-naïve patients with metastatic pancreatic cancer, the modified FOLFIRINOX regimen resulted in a median overall survival of 11.2 months and a response rate of 37.7%, indicating its efficacy in this patient population.

The modified regimen demonstrated a better safety profile compared to previous studies, with a 47.8% incidence of grade 3 or higher neutropenia and fewer serious adverse events, suggesting it can be administered without prophylactic pegfilgrastim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Ozaka, M., Ishii, H., Sato, T., et al.[2019]

In a study of 284 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX, the objective response rates were 14.0% for LAPC and 18.2% for metastatic PDAC, indicating modest effectiveness in both groups.

Median overall survival was 12.7 months for LAPC patients and 8.1 months for metastatic PDAC patients, with significant improvements in 2-year survival probabilities after one year of treatment, highlighting the potential long-term benefits of FOLFIRINOX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Response and Conditional Survival in Advanced Pancreatic Cancer Patients Treated with FOLFIRINOX: A Multicenter Cohort Study. van der Sijde, F., van Dam, JL., Groot Koerkamp, B., et al.[2022]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

Modified FOLFIRINOX for advanced pancreatic cancer showed promising survival rates, with 6-month overall survival at 90.9% for locally advanced cases and 79.7% for metastatic cases, based on a meta-analysis of 11 studies involving 563 patients.

This modified regimen resulted in fewer severe adverse events compared to conventional FOLFIRINOX, suggesting it may be a safer and more tolerable option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Tong, H., Fan, Z., Liu, B., et al.[2022]

In a study of 289 patients with advanced pancreatic ductal adenocarcinoma, the FOLFOXIRI chemotherapy regimen showed similar overall survival (11.1 months) compared to the standard FOLFIRINOX regimen (11.6 months), indicating no significant therapeutic advantage for FOLFOXIRI.

FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events (28.7% vs. 19.5% for FOLFIRINOX), suggesting that while it is feasible, it may lead to more severe side effects without improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. Vienot, A., Chevalier, H., Bolognini, C., et al.[2020]

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

Neoadjuvant FOLFIRINOX treatment in patients with borderline resectable pancreatic cancer (BRPC) resulted in a median overall survival of 22.2 months and a high resection rate of 67.8%, indicating its potential effectiveness in this patient group.

The treatment was associated with manageable adverse events, with the most common being neutropenia, diarrhea, and fatigue, but no deaths were reported due to FOLFIRINOX, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Janssen, QP., Buettner, S., Suker, M., et al.[2021]

Citations

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

Initial Results from the DIRECT Registry Study - PMC The DIRECT Registry study is a prospective trial of irreversible electroporation (IRE) using the NanoKnife System for the treatment of patients with Stage 3 ...

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

Irreversible Electroporation in Pancreatic Cancer—An ... According to the data presented by Bhutiani et al., 2020 [24], the use of stand-alone IRE results in a two-times decrease in the proliferation ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03899649

A Registry Study of NanoKnife IRE for Stage 3 Pancreatic ... This multicenter, observational study will evaluate the effectiveness and safety of the NanoKnife System when used for the ablation of Stage 3 pancreatic ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2210261217304443

Irreversible electroporation for locally advanced pancreatic ... Conclusion. While there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties ...

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

Irreversible Electroporation (NanoKnife) - Medical Clinical ... The early clinical experience with IRE demonstrated safety for the ablation of human liver tumors. Short-term data regarding oncologic outcome is now emerging ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9688427/

Safety and Efficacy of Irreversible Electroporation in Locally ... IRE can kill tumors completely, with well-demarcated borders and tolerance of the heat-sink effect [6,18]. As a radical ablative therapy, IRE ...

7. bmcsurg.biomedcentral.com bmcsurg.biomedcentral.com/articles/10.1186/s12893-025-03136-9

Real-world safety of irreversible electroporation therapy for ... We found that the overall reports of adverse events associated with Nanoknife treatment has been declining. However, gastrointestinal injuries ...