Treatment of primary and secondary liver tumors with an hepatic ablation cool-wet radiofrequency system.

ISRCTN	ISRCTN73194360
DOI	https://doi.org/10.1186/ISRCTN73194360
Protocol serial number	438/13/EC
Sponsor	Parc de Salut Mar- Hospital del Mar
Funder	Health Research Fund (Fondo de Investigación Sanitaria) (FIS PI12/00799)

Submission date: 13/04/2015
Registration date: 14/06/2015
Last edited: 10/07/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Radiofrequency ablation is a cancer treatment that uses heat made by radio waves to kill cancer cells. Radiofrequency is a type of electrical energy that heats up solid tumours and kills it. The aim of this study is to compare a new method we have developed for ablating liver tumours, the hepatic "cool-wet" radiofrequency ablation system with other methods already available. The study also investigates how safe the method is to use (phase 1 of the study) and how effective a treatment it is (phase 2).

Who can participate?
Adults (aged at least 18) with liver cancer (hepatocellular carcinoma and macrotrabecular with <3 lesions of 1.5-4 cm diameter)

What does the study involve?
There are two phases to the study. In phase 1, the safety of “cool-wet” radiofrequency system is tested. In phase 2, participants are randomly allocated into one of two groups. Those in group 1 undergo a conventional hepatic (liver) ablation technique. Those in group 2 are given the new “cool-wet” hepatic radiofrequency ablation system. The clinical outcomes of the two groups of participants are then compared in terms of whether the treated cancer reoccurred.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
The Hospital del Mar (Spain)

When is the study starting and how long is it expected to run for?
January 2012 to June 2020

Who is funding the study?
Health Research Fund (Fondo de Investigación Sanitaria) (Spain)

Who is the main contact?
Dr Rita Quesada
rquesada@imim.es

Contact information

Dr Rita Quesada
Public

Parc de Rerceca Biomèdica de Barcelona
Doctor Aiguader, 88
08003 Barcelona
Barcelona
08003
Spain

Phone	93 316 16 21
Email	rquesada@imim.es

Study information

Primary study design	Interventional
Study design	Interventional prospective randomized parallel-group single-blinded study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Treatment of primary and secondary liver tumors with an hepatic ablation cool-wet radiofrequency system: an interventional single-centre study.
Study acronym	GNOMON
Study objectives	Current study hypothesis as of 17/06/2020: 1. Assess the safety of the radio-frequency ablation with the new device ("cool-wet system" to treat hepatocellular carcinoma and liver metastases between 1.5 - 4 cm of diameter. 2. Verify if the new radio-frequency method is at least as effective than the conventional method in terms of technical success of the lesion and overall survival. The conventional method considers the current technique performed by interventional radiologists and surgeons of the hospital (microwaves) for any of the possible ways of application (percutaneous, laparoscopic or open surgery). Previous study hypothesis: 1. Assess the safety of the radio-frequency ablation with the new device ("cool-wet system" to treat hepatocellular carcinoma and liver metastases between 1.5 - 4 cm of diameter. 2. Verify if the new radio-frequency method is at least as effective than the conventional method in terms of lower recurrence and total ablation of the lesion (single puncture). The conventional method considers the current technique performed by interventional radiologists and surgeons of the hospital (ablation method cool-tip and microwaves) for any of the possible ways of application (percutaneous, laparoscopic or open surgery).
Ethics approval(s)	1. Ethical Committee of Clinical Research of the Hospital del Mar, 27/06/2012, ref: 2012/4776/I 2. Agencia Española del Medicamento y Producto Sanitario, 10/06/2013, ref: 438/13/EC
Health condition(s) or problem(s) studied	Hepatocellular carcinoma and liver metastases between 1.5 - 4 cm of diameter
Intervention	Current interventions as of 15/06/2020: Radio-frequency ablation with a "Cool-wet" radio-frequency system Phase II: Randomized, parallel-group single-blind study 1. Group MWA: Conventional hepatic ablation technique (control group). The method of ablation control is based on microwaves (AMICA) (n=41 patients) 2. Group RFA: New "cool-wet" hepatic radio-frequency ablation system . (n=41 patients) Previous interventions: Radio-frequency ablation with a "Cool-wet" radio-frequency system 1. Phase I: Safety pilot study based on 20 patients. There is no control group 2. Phase II: Randomized, parallel-group single-blind study 2.1. Group 1: Conventional hepatic ablation technique (control group). The method of ablation control is based on microwaves (AMICA). It considers 55 patients 2.2. Group 2: New "cool-wet" hepatic radio-frequency ablation system previously described in Phase I. 55 patients
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Current primary outcome measures as of 15/06/2020: 1. Technical success evaluated as a complete tumor coverage by the ablation zone at 1-month follow-up 2. Local tumour progression after 2 years of follow-up, measured as complete tumor coverage by the ablation zone and the appearance of any tumor focus in contact with ablation zone after 2-years follow-up Previous primary outcome measures: 1. HLR (Hepatic local recurrence): Characterized by a partial response (PR) or disease progression (DP) of the treated target lesion according to RECIST 1.1 VA. in the abdominal CT or MRI at 6 months (maximum tolerance 50 days) and then every 6 months until 5 years. The maximum cutting thickness to evaluated this is 5 mm 2. MDA (Minimum Diameter Ablation): Defined as the smallest diameter of a single ablation measured by an abdominal CT or MRI at 6-months of the procedure. When they have been treated more than one target lesion, the smallest diameter will be considered
Key secondary outcome measure(s)	Current secondary outcome measures as of 17/06/2020: 1. Safety: all treatment-related complications classified according to the Society of Interventional Radiology guidelines by treated tumor basis taking into account the highest grade. Complications recorded during the total follow-up of the patients. 2. Overall survival (OS) measured as the mean survival expressed in months per each group of treatment 3. Short to long diameter ratio (SLR) of the ablation measured from the TAC performed 1 month after the ablation 4. Sphericity ratio (SR) measured as the largest diameter to average of the two remaining diameters of the ablation zone. Ratio close to 1 implies more spherical shape, measured from the TAC performed 1 month after the ablation. 5. Surface area of the coagulation zone measured in cm² from the reconstruction of the coagulation zone (1 month after the ablation) 6. Coefficient of variation (CV) as a measure for reproducibility expressed in % and measured from the reconstruction of the coagulation zone (1 month after the ablation) Previous secondary outcome measures: 1. Maximum diameter of the ablation (anteroposterior, transverse and craniocaudal) 2. Mean volume of the ablation, measured by digital reconstruction from CT or MRI after a month of PO using appropriate image software
Completion date	01/06/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	130
Total final enrolment	102
Key inclusion criteria	1. Nodules suggestive of HCC or liver metastases from any source as abdominal CT, MRI or biopsy. The initial imaging test (CT or MRI) must not be older than 30 days (50 days maximum tolerance). 2. Considered unresectable hepatic nodules in multidisciplinary and capable local treatment session 3. Number of nodes: between 1 and 3 4. Size of the nodules: between 1.5 and 4 cm 5. Percutaneous, laparoscopic or open surgical access. 6. Signature of informed consent 7. Aged at least 18
Key exclusion criteria	1. Higher than third level of Anesthetic risk measured by the classification of the American Association anesthesia (ASA IV) 2. Carrier of a cardiac pacemaker 3. Thrombocytopenia <50,000 / mL 4. Suspicion of thrombosis portal by presence of tumor 5. Child C and grading of hepatic failure 6. Previous biliodigestive anatomosis 7. Hepatic subcapsular nodule
Date of first enrolment	01/06/2015
Date of final enrolment	01/04/2020

Locations

Countries of recruitment

Spain

Study participating centre

Hospital del Mar

-
Spain

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan	The datasets generated during the current study will be available upon request from Dr Rita Quesada (rquesada@imim.es). Part of the database will become available for 2 years to medical researchers. The principal investigator of the study will evaluate the request and will decide which data can be shared.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		10/01/2022	10/07/2023	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

10/07/2023: Publication reference added.
17/06/2020: The following changes were made to the trial record:
1. The total final enrolment number and IPD sharing statement were added.
2. The secondary outcome measures and study hypothesis were updated.
3. The recruitment end date was changed from 01/06/2020 to 01/04/2020.
4. The overall trial end date was changed from 31/12/2021 to 01/06/2020.
5. The intention to publish date was changed from 31/12/2018 to 30/06/2020.
15/06/2020: The following changes were made to the trial record:
1. The study design was changed from 'Interventional single-centre study' to 'Interventional prospective randomized parallel-group single-blinded study'.
2. The interventions and primary and secondary outcome measures were updated.
3. The recruitment start date was changed from 01/01/2013 to 01/06/2015.
05/06/2018: An intention to publish date has been added.
04/06/2018: The following changes have been made:
1. The recruitment end date was changed from 12/05/2018 to 01/06/2020.
2. The overall trial end date was changed from 31/12/2019 to 31/12/2021.
07/03/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2015 to 12/05/2018.
2. The overall trial end date was changed from 01/12/2017 to 31/12/2019.