NanoKnife IRE for Pancreatic Cancer

(DIRECT Trial)

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

528 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares chemotherapy alone to chemotherapy plus an electrical pulse treatment in patients who have responded well to initial chemotherapy. The goal is to see if adding the electrical pulse treatment can better destroy cancer cells. Electrochemotherapy is a method that uses electric pulses to increase the uptake and effectiveness of chemotherapeutic drugs in cancer cells.

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.

What data supports the effectiveness of the treatment NanoKnife IRE for Pancreatic Cancer?

Research shows that a modified version of the FOLFIRINOX regimen, which is part of the treatment, improves safety and survival in patients with locally advanced pancreatic cancer. Additionally, FOLFIRINOX is a standard treatment for advanced pancreatic cancer, indicating its effectiveness in managing the disease. ^{1 2 3 4 5}

Is NanoKnife IRE safe for humans?

The modified FOLFIRINOX regimen, which is related to NanoKnife IRE, has been used in treating pancreatic cancer and is known to cause side effects like neutropenia (low white blood cell count), diarrhea, and fatigue. However, modifications to the regimen have been made to reduce these side effects, making it more tolerable for patients. ^{3 6 7 8 9}

How is the NanoKnife IRE treatment for pancreatic cancer different from other treatments?

The NanoKnife IRE treatment for pancreatic cancer is unique because it combines a modified FOLFIRINOX regimen, which is a chemotherapy treatment, with NanoKnife IRE, a technique that uses electrical pulses to destroy cancer cells. This combination aims to improve safety and effectiveness, especially in patients with locally advanced pancreatic cancer, compared to standard chemotherapy alone. ^{1 2 4 10 11}

Eligibility Criteria

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

Subject is 18 years of age and older

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

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 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]

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]

References

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

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. [2022]

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

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. [2022]

4. China pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. [2020]

5. Egypt pubmed.ncbi.nlm.nih.gov

Treatment Response and Conditional Survival in Advanced Pancreatic Cancer Patients Treated with FOLFIRINOX: A Multicenter Cohort Study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. [2019]

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

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. [2020]

9. England 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. [2022]

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

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. [2021]