NanoKnife for Prostate Cancer

(WIRED Trial)

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Paralysis agents

Disqualifiers: UTI, Bladder neck contracture, IBD, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 day

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on hormonal therapy for prostate cancer, you must stop it at least three months before the procedure.

What data supports the effectiveness of the treatment NanoKnife for prostate cancer?

Research shows that Irreversible Electroporation (IRE), used in the NanoKnife treatment, can effectively target prostate cancer cells while preserving important structures like nerves and blood vessels, which helps reduce side effects such as incontinence or impotence. Studies involving hundreds of patients have demonstrated its safety and ability to maintain quality of life. ^{1 2 3 4 5}

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

The NanoKnife treatment, also known as Irreversible Electroporation (IRE), is unique because it uses electrical pulses to create tiny holes in cancer cell membranes, leading to cell death without using heat, which helps preserve surrounding healthy tissue. This approach is different from traditional treatments like surgery or radiation, which can damage nearby healthy tissues. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to investigate the safety and efficacy of Irreversible Electroporation (IRE) using NanoKnife technology in patients with intermediate-risk prostate cancer. This patient population was chosen because they would otherwise be treated with conventional therapies with high side effects. The main questions it aims to answer are: 1. Is the NanoKnife system is effective at damaging prostate tumour cells, and killing the cancer? 2. Are there any safety concerns with the procedure, or major side effects caused by the treatment? Participants will undergo IRE treatment with the NanoKnife system, and then complete follow-up appointments for 12-months after the procedure.

Eligibility Criteria

This trial is for individuals with intermediate-risk prostate cancer. It's designed for those who might otherwise undergo conventional therapies that come with significant side effects. Participants will be required to attend follow-up appointments for 12 months after the IRE treatment.

Inclusion Criteria

Physician is able to visualize prostate gland adequately on transrectal ultrasound imaging during qualifying biopsy

I am over 50 years old.

My biopsy shows a Gleason score of 7 in targeted areas with no higher scores elsewhere.

Exclusion Criteria

Is unfit for pelvic MRI scanning (e.g., severe claustrophobia, permanent cardiac pacemaker, metallic implants that are likely to contribute significant image artifacts, allergy or contraindication to gadolinium (to enhance MRI)

I haven't had cancer treatment in the last 3 years, except for prostate or skin cancer.

I am interested in preserving my ability to have children.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo IRE treatment with the NanoKnife System under general anesthesia

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1, 3, 6, 9, and 12 months post-procedure

12 months

5 visits (in-person)

Long-term follow-up

Evaluation of longer-term effectiveness of focal IRE and possible delayed adverse events

5 years

Treatment Details

Interventions

• Irreversible Electroporation (NanoKnife)

Trial Overview The trial is testing the safety and effectiveness of a procedure called Irreversible Electroporation (IRE) using NanoKnife technology on prostate tumor cells in patients with intermediate-risk prostate cancer.

Participant Groups

Group I: IRE Treatment Arm Experimental Treatment 1 Intervention

All patients enrolled in this trial will receive IRE treatment with the NanoKnife System.

Irreversible Electroporation (NanoKnife) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as NanoKnife for:

• Prostate cancer

Approved in United States as NanoKnife for:

• Prostate cancer
• Pancreatic cancer
• Liver cancer

Approved in Canada as NanoKnife for:

• Prostate cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Focal irreversible electroporation (IRE) for localized prostate cancer showed excellent oncological outcomes, with a 3-year failure-free survival rate of 96.75% and a 100% overall survival rate among 123 patients followed for a median of 36 months.

The treatment had minimal impact on quality of life, as 98.8% of patients remained pad-free and 76% reported no change in erectile function after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort. Blazevski, A., Scheltema, MJ., Yuen, B., et al.[2021]

Irreversible Electroporation (IRE) is a safe and effective treatment for prostate cancer, showing comparable 5-year recurrence rates to standard radical prostatectomy while preserving urinary continence in all patients and resulting in only mild to moderate adverse effects.

In a study of 471 IRE treatments across 429 patients, IRE demonstrated versatility by being applicable for focal therapy, whole-gland ablation, and recurrent cases, making it a suitable option for various stages of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments. Guenther, E., Klein, N., Zapf, S., et al.[2020]

Irreversible electroporation (IRE) for prostate cancer treatment showed promising short-term results, with a 39% reduction in PSA levels and 84% of primary lesions cleared on MRI after treatment in a study of 45 patients.

The procedure was found to be safe, with no serious complications reported, and it effectively managed both primary and salvage cases of prostate cancer, indicating its potential as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal Irreversible Electroporation for Localized Prostate Cancer - Oncological and Safety Outcomes Using mpMRI and Transperineal Biopsy Follow-Up. Gielchinsky, I., Lev-Cohain, N.[2023]

Irreversible electroporation (IRE) shows potential as a non-thermal treatment for prostate cancer, but its effectiveness remains unproven due to a lack of adequate clinical trials and data specific to tumor types.

The increasing use of IRE outside of clinical trials, driven by media promotion and patient demand, raises concerns about the potential for misleading information and the risk of delaying more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irreversible electroporation. Current value for focal treatment of prostate cancer]. Wendler, JJ., Ganzer, R., Hadaschik, B., et al.[2018]

In a study of 13 male patients with low-risk prostate cancer, irreversible electroporation (IRE) was performed, showing that the ablation area appeared either homogeneously or heterogeneously hypo attenuating on MRI, indicating different responses to the treatment.

Most patients exhibited a peripheral contrast enhancement after IRE, suggesting reactive hyperemia, which may indicate ongoing vascularization in the treated area, highlighting the need for careful imaging follow-up post-ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of irreversible electroporation of prostate cancer on microcirculation: Imaging findings in contrast-enhanced T1-weighted 3D MRI. Beyer, LP., Pregler, B., Verloh, N., et al.[2018]

A CRISPR-Cas9-based genome-editing nanomedicine targeting the EphA2 receptor has been developed to treat castration-resistant prostate cancer (CRPC), showing effectiveness in suppressing tumor cell migration.

The nanoparticle system, RNP@CaP-TAT, demonstrated good biocompatibility and a simple synthesis process, indicating its potential as a promising gene therapy strategy not only for CRPC but also for other cancers with similar gene expression profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy. Wei, CG., Zhang, R., Wei, LY., et al.[2023]

Preclinical models of castration-resistant prostate cancer (CRPC) demonstrated that certain genetic defects in homologous recombination repair (HRR) can predict enhanced sensitivity to treatments like olaparib and cisplatin, suggesting that mutation analysis alone may overlook many patients who could benefit from these therapies.

Patient-derived tumor organoids (PDOs) from CRPC patients closely resemble primary tumors and confirmed the increased effectiveness of olaparib, which also reduced cell migration, highlighting their potential for personalized treatment strategies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical patient-derived modeling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease. Elsesy, ME., Oh-Hohenhorst, SJ., Oing, C., et al.[2023]

A newly identified enhancer located near the androgen receptor (AR) gene contributes to therapeutic resistance in advanced prostate cancer by increasing AR activity, which can lead to cancer cell proliferation even in low androgen conditions.

Using genome editing to disrupt this enhancer reduced cancer cell growth and AR levels, highlighting a potential therapeutic target for overcoming resistance to treatments like enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer. Takeda, DY., Spisák, S., Seo, JH., et al.[2023]

In a study of 23 patient-derived xenografts, it was found that neuroendocrine prostate cancer (NEPC) can develop independently of androgen deprivation treatment, indicating that resistance to AR signaling inhibitors (ARSis) does not require the absence of androgen receptor (AR) expression.

The research revealed that the emergence of a double-negative prostate cancer (DNPC) phenotype can occur without AR expression, even in the presence of mutations in key tumor suppressor genes like PTEN and TP53, suggesting that AR loss and NE differentiation are not directly linked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance to androgen receptor signaling inhibition does not necessitate development of neuroendocrine prostate cancer. Brennen, WN., Zhu, Y., Coleman, IM., et al.[2022]

Niraparib (NIRA) is an effective treatment for patients with metastatic castration-resistant prostate cancer who have specific genetic alterations, showing promising results in a Phase II study.

When combined with abiraterone acetate and prednisone, NIRA demonstrated a manageable safety profile while effectively disrupting cancer cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. Chi, KN., Fleshner, N., Chiuri, VE., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort. [2021]

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

Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Focal Irreversible Electroporation for Localized Prostate Cancer - Oncological and Safety Outcomes Using mpMRI and Transperineal Biopsy Follow-Up. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Irreversible electroporation. Current value for focal treatment of prostate cancer]. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of irreversible electroporation of prostate cancer on microcirculation: Imaging findings in contrast-enhanced T1-weighted 3D MRI. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy. [2023]

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

Preclinical patient-derived modeling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease. [2023]

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

A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer. [2023]

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

Resistance to androgen receptor signaling inhibition does not necessitate development of neuroendocrine prostate cancer. [2022]

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

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. [2023]