Clinical trial NCT03841305: Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Metastasis Colon Cancer
Keywords: Liver
Interventional radiology
Portal vein embolization
Portal and hepatic vein embolization
Future liver remnant
Surgery
Non-cirrhotic liver
Liver metastases
Colorectal cancer
Liver Regeneration
Liver resection
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Federation Francophone de Cancerologie Digestive
First posted: 2019-02-15
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: increase in volume of the future remnant liver (FRL)
timeFrame: at 3 weeks after liver venous deprivation (LVD) or portal vein embolization (PVE) using MRI or CT-scan
Secondary outcomes:
measure: Tolerance
timeFrame: between the day of liver preparation and 90 days after surgery
measure: Post-operative mortality
timeFrame: 90 days after surgery
measure: Post-operative morbidity
timeFrame: 90 days after surgery
measure: Post-hepatectomy liver failure
timeFrame: between the day of the surgery and 90 days after surgery
measure: Rate of non-resectability due to insufficient FRL
timeFrame: between the day of the treatment and the day of the surgery
measure: Rate of non-resectability due to tumor progression
timeFrame: between the day of the treatment and the day of the surgery
measure: Rate of per-operative difficulties
timeFrame: between the day of the surgery and 90 days after surgery
measure: Blood loos, operating time, transfusion
timeFrame: the day of the surgery
measure: R0 resection rate
timeFrame: the day of the surgery
measure: R1 resection rate
timeFrame: the day of the surgery
measure: Pre and post-operative liver volumes
timeFrame: Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
measure: Recurrence-free survival
timeFrame: 90 days after surgery
measure: Overall survival
timeFrame: Between the liver preparation and 90 days after surgery
measure: Evaluation of pre and post-operative liver function
timeFrame: Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
measure: To search for biomarkers predictive of liver hypertrophy/regeneration and immune cell response
timeFrame: The day of liver preparation, on day 1, day 2 and day 3 after liver preparation and the day of surgery
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHU de Montpellier
state: Hérault
city: Angers
country: France
facility: CHU d'Angers
city: Bordeaux
country: France
facility: Bordeaux University Hospital
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Lyon
country: France
facility: Centre Léon Berard
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: APHP - Cochin hospital
city: Poitiers
country: France
facility: CHU de Poitiers
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References:
citation: Deshayes E, Piron L, Bouvier A, Lapuyade B, Lermite E, Vervueren L, Laurent C, Pinaquy JB, Chevallier P, Dohan A, Rode A, Sengel C, Guillot C, Quenet F, Guiu B. Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases. BMC Cancer. 2020 Jun 19;20(1):574. doi: 10.1186/s12885-020-07065-z.