Efficacy and Safety of IRE for RMs

Kidney Cancer Clinical Trial

Official title:

The Efficacy and Safety of Irreversible Electroporation for the Ablation of Renal Masses: A Prospective, Human, In-Vivo Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02298608
• Other study ID #: NL 44785.018.13
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: November 20, 2014
• Last updated: November 21, 2014
• Start date: January 2014
• Est. completion date: December 2016

Study information

• Verified date: November 2014
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Prof. M. Pilar Laguna Pes, M.D. Ph.D.
• Phone: +31(0)20-5668637
• Email: m.p.lagunapes[@]amc.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial Summary

Background:

Electroporation or electropermeabilisation is a novel technique with the potential to overcome the main disadvantages of thermal ablation. It utilizes electric pulses, traveling between two or more electrodes, to create 'nanopores' in the cell membrane. If the applied current reaches a certain threshold these 'nanopores' become permanent resulting in cell death. The use of electric current means that IRE is not susceptible to 'thermal sink' leading to consistent ablation results. IRE ablation targets the cell membrane, sparing tissue architecture and minimizing damage to blood vessels, nerves and the renal collecting system.

The first in human studies have proven the safety of IRE for the ablation of small renal masses. However the efficacy of IRE through histopathological examination of an ablated renal tumour has not yet been studied, compromising the correct and scientific evaluation of this new technology.

Primary Objectives:

• To determine the efficacy of IRE ablation of renal masses , measured by histopathologic examination of the targeted tumour.

• To determine the safety of IRE ablation of renal masses, by evaluating device and procedural adverse events.

Secondary Objectives:

• To evaluate the efficacy of MRI in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation.

• To evaluate the efficacy of CEUS in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation.

Population:

10 patients, age ≥ 18 years, presenting with a solid enhancing mass, who are candidates for radical nephrectomy.

Intervention:

Eligible patients will receive IRE ablation of their renal mass 4 weeks prior to radical nephrectomy. Follow-up at one and four weeks post IRE will be performed using MRI and CEUS imaging. After radical nephrectomy histopathological examination will be performed to evaluate IRE ablation success.

Description:

Rationale:

The past decades have shown an increase in the incidence of small renal masses (SRM). At the moment laparoscopic partial nephrectomy is the 'golden standard' in treatment of SRMs. Thermal ablation techniques are indicated in patients who are poor surgical candidates or who have a predisposition to develop multiple tumours. Recent studies have shown thermal ablation techniques to have similar long-term oncologic results. Downsides to thermal ablation are the possible damage to vital structures in the vicinity of the ablation zone, e.g. collecting system or intestine, and unpredictable results due to difficulty in monitoring the ablation zone and 'thermal sink'.

Electroporation or electropermeabilisation is a novel technique with the potential to overcome the main disadvantages of thermal ablation. It utilizes electric pulses, traveling between two or more electrodes, to create 'nanopores' in the cell membrane. If the applied current reaches a certain threshold these 'nanopores' become permanent resulting in cell death. The use of electric current means that IRE is not susceptible to 'thermal sink' leading to consistent ablation results. IRE ablation targets the cell membrane, sparing tissue architecture and minimizing damage to blood vessels, nerves and the renal collecting system.

The first in human studies have proven the safety of IRE for the ablation of small renal masses. However the efficacy of IRE through histopathological examination of an ablated renal tumour has not yet been studied, compromising the correct and scientific evaluation of a new technology. This is the primary objective of this research project.

Objectives:

Primary Objectives:

• To determine the efficacy of IRE ablation of renal masses , measured by histopathologic examination of the targeted tumour.

• To determine the safety of IRE ablation of renal masses, by evaluating device and procedural adverse events.

Secondary Objectives:

• To evaluate the efficacy of MRI in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation.

• To evaluate the efficacy of CEUS in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation.

Study design:

This is a prospective, human, in-vivo pilot study. Study population: 10 patients, age ≥ 18 years, presented with a solid enhancing RM , who are candidates for radical nephrectomy.

Intervention:

Patients will receive IRE ablation of the RM, performed under general anaesthesia, 4 weeks before radical nephrectomy. Follow-up at one and four weeks post IRE will be performed using MRI and CEUS imaging. After radical nephrectomy histopathological examination will be performed to evaluate IRE ablation success.

Main study parameters/endpoints:

Primary endpoints:

• The efficacy of IRE ablation of renal masses , measured by histopathologic examination of the targeted tumour by an experienced genitourinary pathologist. Using immunehistochemical staining to evaluate cell viability.

• The safety of IRE ablation of renal masses, by evaluating device and procedural adverse events using CTCAE v4.0.

Secondary endpoints:

• The efficacy of MRI in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation. By comparing MRI imaging to the histopathological examination results of the resected material.

• The efficacy of CEUS in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation. By comparing CEUS imaging to the histopathological examination results of the resected material.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

There are no benefits for patients that participate in this study. Study participants will be exposed to additional risk when compared to standard treatment. They will have to undergo an additional procedure under general anaesthesia with muscle relaxation. The exposure to ionizing radiation during the procedure has been estimated at 32 mSv. Patients have to be informed about the risks of procedural complications. Information on the efficacy of IRE, proven histopathologically, is a vital step in order to progress to long term follow-up studies without tumour excision. So far no study has investigated the efficacy of IRE for the ablation of renal tumours in this manner.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Solid, enhancing mass on cross sectional imaging

• Scheduled for a radical nephrectomy, open or laparoscopic.

• Signed informed consent

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

• Severe cardiovascular disease in medical history

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Device:
• Nano Knife
Percutaneous, CT guided, ablation of renal mass

Locations

Country	Name	City	State
Netherlands	Dept. Urology, Academic Medical Center, Amsterdam	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The efficacy of IRE ablation of renal masses , measured by histopathologic examination of the targeted tumour by an experienced genitourinary pathologist. Using immunehistochemical staining to evaluate cell viability.		1 month	No
Primary	Number of device and procedural adverse events using CTCAE v4.0.		1 month	Yes
Secondary	The efficacy of MRI in the imaging of ablation success	The efficacy of MRI in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation. By comparing MRI imaging to the histopathological examination results of the resected material.	1 month	No
Secondary	The efficacy of CEUS in the imaging of ablation success	The efficacy of CEUS in the imaging of ablation success, extend of the ablation zone, one and four weeks post IRE ablation. By comparing CEUS imaging to the histopathological examination results of the resected material.	1 month	No