Safety and Feasibility of IRE for SRMs

Study Overview
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Brief Summary
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Irreversible Electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality. The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumours. This is a prospective, human, in-vivo study among 20 patients presenting with solid enhancing SRM on cross sectional imaging suspect for renal cell carcinoma (RCC). Preoperatively, imaging is required through Magnetic Resonance Imaging (MRI), Contrast-enhanced ultrasound (CEUS) and contrast-enhanced Computed Tomography (CT). Furthermore, serum creatinine levels and VAS scores are obtained. A biopsy of the SRM will be performed in preoperative setting. IRE ablation will be performed using CT-guidance and ablation success will be measured directly after the ablation through contrast-enhanced CT. Device related adverse events (AE) will be registered using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 guideline. One week post ablation only CEUS and MRI will be performed to limit exposure to ionizing radiation. At 3 months, 6 months and 12 months post ablation CEUS, MRI and CT will be performed. Additionally, at these time points serum creatinine levels and VAS scores will be obtained, and quality of life will be assessed through SF-36 questionnaires. Residual and recurrent disease will be assessed through tissue enhancement on cross sectional imaging.

Official Title
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The Safety and Feasibility of Irreversible Electroporation for the Ablation of Small Renal Masses

Conditions
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Kidney Cancer

Intervention / Treatment
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* Device: Irreversible Electroporation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Solid, enhancing mass on cross sectional imaging Signed informed consent Candidate for focal ablative therapy Exclusion Criteria: Irreversible bleeding disorders Inability/unwillingness to interrupt anticoagulation therapy Previous cryoablation, RFA or partial nephrectomy in affected kidney Anaesthesia Surgical Assignment (ASA), category ≤ IV ICD / pacemaker

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irreversible electroporation (IRE)<br>IRE is based on high current electric pulses, transferred between two or more placed needle electrodes. Charging the cell membrane causes holes in the cell membrane called nanopores, resulting in increased permeability of the cell and subsequent cell death. | Device: Irreversible Electroporation<br>* Guided by CT and accompanied by an external spacer for fixation, needle electrodes will be placed. The amount of probes and probe placement will be attuned for specific tumour size and location, granting 15mm between the electrodes with an active tip length of 15mm. IRE pulses with pulse intensity of 1500 V/cm will be delivered in 90 consecutive pulses of 90µs.<br>* Other names: Nanoknife;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety IRE ablation procedure (evaluating device and procedural adverse events using CTCAE v4.0) | To determine the safety and feasibility of IRE ablation of small renal masses (≤ 4cm), by evaluating device and procedural adverse events using CTCAE v4.0 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy ((non-)presence of tumour enhancement on cross-sectional imaging post IRE) | To determine the clinical efficacy of IRE ablation of small renal masses (≤ 4cm), assessed by calculating recurrence and residual disease at follow-up, measured through the (non-)presence of tumour enhancement on cross-sectional imaging post IRE | 2 years | 
| Cross sectional imaging post ablation | To evaluate the use of CT, MRI, and CEUS in the imaging of ablation success, extend of the ablation zone, 1 week, 3 months, 6 months, and 1 year post IRE | 2 years | 
| Renal function | To evaluate the effect of RE ablation of small renal masses (≤ 4cm) on the renal function, measured by serum creatinine levels and estimated Glomerular Filtration Rate (eGFR) | 2 years | 
| Average length of hospital stay | To evaluate the effect of IRE ablation of small renal masses (≤ 4cm) on the length of hospital stay, measured in average stay in days | 2 years | 
| Quality of Life | To evaluate the effect of IRE ablation of small renal masses (≤ 4cm) on the quality of life, assessed through SF-36 questionnaires | 2 years | 
| Postoperative pain score | To asses the effect of IRE ablation of small renal masses (≤ 4cm), assessed through VAS score and analgesics use | 1 year |