Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant

Liver Metastasis Colon Cancer Clinical Trial

— HYPER-LIV01  

Official title:

Simultaneous Portal and Hepatic Vein Embolization Versus Portal Vein Embolization for Hypertrophy of the Future Liver Remnant Before Major Hepatectomy of Non-cirrhotic Liver : a Multicentric Comparative Randomized Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03841305
• Other study ID #: RECHMPL18_0025
• Secondary ID: UF 7595
• Status: Recruiting
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: April 2024

Study information

• Verified date: May 2023
• Source: University Hospital, Montpellier
• Contact: Boris GUIU, MD
• Phone: 0467337546
• Email: b-guiu[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The hypothesis is that liver venous deprivation (LVD) could strongly improve hypertrophy of the future remnant liver (FRL) at 3 weeks, as compared to portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.

Description:

Portal vein embolization (PVE) has been widely used to generate hypertrophy of the nonembolized lobe in patients undergoing major hepatectomy in order to prevent small-for-size remnant liver resulting in post-operative liver insufficiency.

Although PVE is a safe and effective procedure, it does not always induce sufficient hypertrophy of the future remnant liver (FRL) even after a long time. In case of insufficient liver regeneration following PVE, some authors suggested to embolize hepatic vein(s) (Hwang, Ann Surg 2009).

Interestingly, the sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FRL. Although attractive, this approach requires two different procedures and does not spare time as compared to PVE alone.

To shorten and optimize the phase of liver preparation before surgery,the so-called liver venous deprivation (LVD) technique that combines both PVE and HVE during the same procedure was developed.

The aim of this randomized phase II trial is to compare the percentage of change in FRL volume at 3 weeks after LVD or PVE using MRI or CT-scan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: April 2024
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Liver metastases from colo-rectal origin considered as resectable (as validated by a multidisciplinary committee with at least one senior hepatic surgeon) provided sufficient FRL volume

• Percentage of FRL volume < 30%

• Age = 18 years

• General health status World Health Organisation 0,1

• Estimated life expectancy > 3 months

• Patients whose biological parameters are :

• Platelets =100,000/mm3,

• Polynuclear neutrophils = 1000/mm3,

• Hemoglobin= 9g/dL (even transfused patients can be included)

• Creatininemia < 1.5 times the normal value

• Creatinine clearance > 30 milliliters (mL)/min

• Bilirubinemia = 1,5 times the normal value

• liver transaminases = 5 times the normal value

• prothrombin rate > 70%

• Reference liver CT-Scan or MRI done during the 30 days preceding PVE or LVD.

• Written informed consent

• National health insurance cover

Exclusion criteria

• Patient with cirrhosis

• Presence of clinical ascites

• Ongoing participation or participation within the 21 days prior to inclusion in the study in another therapeutic trial with an experimental drug

• Serious non-stabilized disease, active uncontrolled infection or other serious underlying disorder likely to prevent the patient from receiving the treatment

• Pregnancy (betaHCG positive), breast-feeding or the absence of effective contraception for women of child-bearing age

• Contraindication for the MRI : Pacemaker or neurosensorial stimulator or implantable defibrillator, cochlear implant, ferromagnetic foreign body similar to the nervous structure.

• Allergy or contra-indication to iodine contrast agents (thyrotoxicosis, allergy to the active substance or excipients)

• Treatment with anticoagulants (heparin or AVK) that cannot be interrupted for 48 hours

• Treatment with anti-platelets that cannot be interrupted for 5 days for aspirin or Plavix

• Legal incapacity (persons in custody or under guardianship)

• Deprived of liberty Subject (by judicial or administrative decision)

• Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social or psychological reasons

Related Conditions & MeSH terms

• Hypertrophy
• Liver Metastasis Colon Cancer
• Neoplasm Metastasis

Intervention

Procedure:
• Liver preparation before major hepatectomy
Simultaneous portal and hepatic vein embolization versus Portal vein embolization, also called venous deprivation OR portal vein embolization.

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	Bordeaux University Hospital	Bordeaux
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	Centre Léon Berard	Lyon
France	Hospices Civils de Lyon	Lyon
France	CHU de Montpellier	Montpellier	Hérault
France	CHU de Nice	Nice
France	APHP - Cochin hospital	Paris
France	CHU de Poitiers	Poitiers
France	Hôpital Paul Brousse	Villejuif
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	increase in volume of the future remnant liver (FRL)	The primary outcomes is to compare the increase in volume of the future remnant liver (FRL)	at 3 weeks after liver venous deprivation (LVD) or portal vein embolization (PVE) using MRI or CT-scan
Secondary	Tolerance	Toxicities are evaluated according to NCI-CTCAE version 4.03 published 14 June 2010	between the day of liver preparation and 90 days after surgery
Secondary	Post-operative mortality	Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay	90 days after surgery
Secondary	Post-operative morbidity	Post-operative morbidity defined as the percentages of grade I/II/III/IV/V complications according to Clavien-Dindo classification within the 90 days after surgery or within the hospital stay.	90 days after surgery
Secondary	Post-hepatectomy liver failure	Post-hepatectomy liver failure defined according to the "50-50" criteria or peak bilirubin >7mg/dL.	between the day of the surgery and 90 days after surgery
Secondary	Rate of non-resectability due to insufficient FRL	Rate of non-resectability due to insufficient FRL defined as the percentage of patients for whom resection will be not attempted due to insufficient FRL	between the day of the treatment and the day of the surgery
Secondary	Rate of non-resectability due to tumor progression	Rate of non-resectability due to tumor progression defined as the percentage of patients for whom resection will not be attempted due to tumor progression.	between the day of the treatment and the day of the surgery
Secondary	Rate of per-operative difficulties	Rate of per-operative difficulties defined as the percentage of patients for whom per-operative difficulties are encountered by the surgeon	between the day of the surgery and 90 days after surgery
Secondary	Blood loos, operating time, transfusion	Blood loss are evaluated in mL. Operating time avec evaluated in minutes and transfusion are evaluated by number of packed red blood cells	the day of the surgery
Secondary	R0 resection rate	Rate of R0 resection defined as no microscopic tumor residual	the day of the surgery
Secondary	R1 resection rate	Rate of R1 resection defined as the percentage of patients resected with margin <1mm	the day of the surgery
Secondary	Pre and post-operative liver volumes	Pre and post-operative liver volumes will be evaluated through CT or MRI acquisitions by calculating whole liver, tumor and FRL volumes	Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
Secondary	Recurrence-free survival	Recurrence-free survival defined as the time from date of randomization to date of recurrence or death from their tumor. Patients alive will be censored at the date of last news.	90 days after surgery
Secondary	Overall survival	Overall survival defined as the time from date of randomization to date of death from any cause. Patients alive will be censored at the date of last news.	Between the liver preparation and 90 days after surgery
Secondary	Evaluation of pre and post-operative liver function	Evaluation of pre and post-operative liver function will be evaluated using 99mTc mebrofenine scintigraphy through SPECT/CT acquisitions by calculating mebrofenin clearance in %/min/m² of whole liver and FRL at the same time points as CT/MRI	Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
Secondary	To search for biomarkers predictive of liver hypertrophy/regeneration and immune cell response	Biomarkers predictive of liver hypertrophy/regeneration are evaluated by blood samples and liver biopies	The day of liver preparation, on day 1, day 2 and day 3 after liver preparation and the day of surgery