Irreversible Electroporation of Unresectable Liver Tumors

Irreversible Electroporation of Unresectable Liver Tumors - a Phase I Study of Safety and Feasibility

The aim of this study is to evaluate the safety and feasibility of curative intended irreversible electroporation (IRE) in the treatment of liver tumors neighboring major vessels or bile ducts.

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma; Bile Duct Cancer; Liver Metastases
• Intervention / Treatment: Procedure: Irreversible electroporation

Detailed Description

Patients can be included in the study if they have one or more malignant liver tumors unsuitable for resection and thermal ablation (due to proximity of major vessels or bile duct) or other established liver directed therapies.

Prior to inclusion all potential participant will be evaluated by the local multidisciplinary team, to insure fulfillment of the above-mentioned criteria. In general, the included patient will have tumors with <1 cm of margin to major hepatic vessels or bile ducts, thereby not allowing for conventional treatments because of risk of i.e. hemorrhage, biliary tract damage, liver failure or ineffective ablation due to heat sink.

IRE will be done under general anesthesia as an in-patient procedure. Patients will be observed for at least 24 hours after IRE.

Patients will attend CT scans 1, 3, 6, 9, 12, 18, 24, 36, 48 and 60 months post-IRE according to national guidelines (for follow-up after radiofrequency ablation (RFA)). Patients will attend the out-patient clinic after 1, 3, 6, 9, 12, 18 and 24 months. During the follow-up period, patients will be asked to fill out electronic forms monitoring pain, quality of life and nutritional status. After 24 months the patients will only be followed with CT scans in accordance with the mentioned schedule. Data collection for scientific purposes will stop when the last included patient has been followed for at least 24 months or when the study period concludes.

In case of multiple liver tumors, where a conventional treatment approach is not possible due to a single lesion being too close to major vessels or bile ducts, IRE may be used in conjunction to conventional therapy.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Gastrointestinal Surgery, Aalborg University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary or secondary cancer of the liver.
• Largest tumor diameter ≤5 cm in any plane.
• Tumor must be deemed as unresectable and unsuitable for other established curative liver directed therapies.
• Treatment must be given with curative intent.
• Patients must be able to give informed consent.

Exclusion Criteria:

• Radiological signs of synchronous intra- or extrahepatic disease, unless curative intended therapy is planned.
• Tumor is inaccessible e.g. due to venous dilation etc. (assessed with preoperative ultrasound)
• American Society of Anesthesiologists (ASA) score >3
• Eastern Cooperative Oncology Group (ECOG) performance status >2
• Child-Pugh class C
• International Normalized Ratio (INR)>1.5
• Pregnancy
• Persistent atrial fibrillation
• Implanted electronic devices e.g. cardiac pacemakers or other electrostimulators.
• Metal stents or other metallic objects near the ablation zone (unless the stent can be replaced with a plastic stent prior to IRE)
• Severe allergies to anesthetic agent, paralytic agent or any of the equipment used during treatment.
• Patient is referred from a hospital outside of Denmark

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Selected patients who choose to participate will undergo ablation of the target lesion using irreversible electroporation.	Procedure: Irreversible electroporation; The IRE procedure will be carried out as ultrasound guided technique either percutaneously or during laparotomy. Needle spacing and electrical pulse delivery will be performed in a standardized way.; Other Names: NanoKnife(TM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day complication rate and severity	Adverse events will be registered and scaled according to the Clavien-Dindo classification.	90 days after intervention (last patient)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success rate	The rate of patients were it is possible to place needles according to the treatment plan and deliver 90 electrical pulses per electrode pair	90 days after intervention (last patient)
Technical efficacy rate (1 month) (according to SIR)	The rate of patients showing no residual tumor on contrast enhanced computed tomography (ceCT)	90 days after intervention (last patient)
Median local progression free survival from IRE	The median time from the intervention to progressive disease of the treated lesion, according to RECIST 1.1 or modified RECIST (mRECIST) (only for HCC).	2 years after intervention (last patient)
Median overall survival (OS) from IRE	The median time from the intervention to death.	2 years after intervention (last patient)
Longitudinal changes in perceived quality of life	Quality of life questionnaire - Core 30 is used to assess the quality of life in the included patients. Raw scores will be calculated according to the manual. Items will be grouped in: Global health status (range 0 - 100, high is good), Functional scales (range 0 - 100, high is good) and symptom scales (range 0 - 100 low is good). Differences in each scales during the course of the trial will be calculated separately.	2 years after intervention (last patient)
Longitudinal changes in pain perception	Long term pain will be assessed using the modified Danish version of the Brief Pain Inventory - short form. The outcomes assessed will be an average score of pain severity items and interference items in accordance with the manual. The scales range from 0 to 10 (lower is less pain).	2 years after intervention (last patient)
Periprocedural pain perception	Perioperative pain will be scores using the visual analogue pain scale (range 0 - 10, low score is less pain).	90 days after intervention (last patient)
Longitudinal changes in Eastern Cooperative Oncology Group (ECOG) performance status	Physicians assessment of global functioning using the "Eastern Cooperative Oncology Group" performance status scale (range 0 - 5, low score is better)	2 years after intervention (last patient)
Longitudinal changes in nutritional status assessment	Nutritional status assessment using the Scored Patient-Generated Subjective Global Assessment (short form). The short form includes only patient reported measures and will be combined into a single score according to the manual (range 0 - 37, low score is better).	2 years after intervention (last patient)

Collaborators and Investigators

• Sponsor: Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery
• Investigators: Study Director: Ole Thorlacius-Ussing, Professor, DMSc, Department of Gastrointestinal Surgery, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): March 30, 2025
• Study Completion (Anticipated): March 30, 2025

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 25, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 24, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: ablation; irreversible electroporation; IRE; NanoKnife; colorectal liver metastases; primary liver cancer; secondary liver cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Neoplastic Processes; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Neoplasm Metastasis; Cholangiocarcinoma; Bile Duct Neoplasms
• Other Study ID Numbers: N-20190072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes