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Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant (HYPER-LIV01)

Primary Purpose

Liver Metastasis Colon Cancer

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Liver preparation before major hepatectomy
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Metastasis Colon Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de MontpellierRecruiting
  • CHU d'AngersRecruiting
  • Bordeaux University HospitalRecruiting
  • CHU de Dijon
  • CHU de Grenoble
  • Hospices Civils de LyonRecruiting
  • Centre Léon Berard
  • CHU de NiceRecruiting
  • APHP - Cochin hospitalRecruiting
  • CHU de Poitiers
  • Hôpital Paul Brousse
  • Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

portal vein embolization

liver venous deprivation

Arm Description

Liver preparation before major hepatectomy : portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.

Liver preparation before major hepatectomy : Patients with the liver venous deprivation (LVD) technique that combines both PVE and hepatic vein embolization (HVE) during the same procedure.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Tolerance
Toxicities are evaluated according to NCI-CTCAE version 4.03 published 14 June 2010
Post-operative mortality
Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay
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.
Post-hepatectomy liver failure
Post-hepatectomy liver failure defined according to the "50-50" criteria or peak bilirubin >7mg/dL.
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
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.
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
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
R0 resection rate
Rate of R0 resection defined as no microscopic tumor residual
R1 resection rate
Rate of R1 resection defined as the percentage of patients resected with margin <1mm
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
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.
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.
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
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

Full Information

First Posted
February 13, 2019
Last Updated
May 2, 2023
Sponsor
University Hospital, Montpellier
Collaborators
Federation Francophone de Cancerologie Digestive
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1. Study Identification

Unique Protocol Identification Number
NCT03841305
Brief Title
Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 29, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier
Collaborators
Federation Francophone de Cancerologie Digestive

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
portal vein embolization
Arm Type
Active Comparator
Arm Description
Liver preparation before major hepatectomy : portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.
Arm Title
liver venous deprivation
Arm Type
Experimental
Arm Description
Liver preparation before major hepatectomy : Patients with the liver venous deprivation (LVD) technique that combines both PVE and hepatic vein embolization (HVE) during the same procedure.
Intervention Type
Procedure
Intervention Name(s)
Liver preparation before major hepatectomy
Intervention Description
Simultaneous portal and hepatic vein embolization versus Portal vein embolization, also called venous deprivation OR portal vein embolization.
Primary Outcome Measure Information:
Title
increase in volume of the future remnant liver (FRL)
Description
The primary outcomes is to compare the increase in volume of the future remnant liver (FRL)
Time Frame
at 3 weeks after liver venous deprivation (LVD) or portal vein embolization (PVE) using MRI or CT-scan
Secondary Outcome Measure Information:
Title
Tolerance
Description
Toxicities are evaluated according to NCI-CTCAE version 4.03 published 14 June 2010
Time Frame
between the day of liver preparation and 90 days after surgery
Title
Post-operative mortality
Description
Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay
Time Frame
90 days after surgery
Title
Post-operative morbidity
Description
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.
Time Frame
90 days after surgery
Title
Post-hepatectomy liver failure
Description
Post-hepatectomy liver failure defined according to the "50-50" criteria or peak bilirubin >7mg/dL.
Time Frame
between the day of the surgery and 90 days after surgery
Title
Rate of non-resectability due to insufficient FRL
Description
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
Time Frame
between the day of the treatment and the day of the surgery
Title
Rate of non-resectability due to tumor progression
Description
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.
Time Frame
between the day of the treatment and the day of the surgery
Title
Rate of per-operative difficulties
Description
Rate of per-operative difficulties defined as the percentage of patients for whom per-operative difficulties are encountered by the surgeon
Time Frame
between the day of the surgery and 90 days after surgery
Title
Blood loos, operating time, transfusion
Description
Blood loss are evaluated in mL. Operating time avec evaluated in minutes and transfusion are evaluated by number of packed red blood cells
Time Frame
the day of the surgery
Title
R0 resection rate
Description
Rate of R0 resection defined as no microscopic tumor residual
Time Frame
the day of the surgery
Title
R1 resection rate
Description
Rate of R1 resection defined as the percentage of patients resected with margin <1mm
Time Frame
the day of the surgery
Title
Pre and post-operative liver volumes
Description
Pre and post-operative liver volumes will be evaluated through CT or MRI acquisitions by calculating whole liver, tumor and FRL volumes
Time Frame
Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
Title
Recurrence-free survival
Description
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.
Time Frame
90 days after surgery
Title
Overall survival
Description
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.
Time Frame
Between the liver preparation and 90 days after surgery
Title
Evaluation of pre and post-operative liver function
Description
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
Time Frame
Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery
Title
To search for biomarkers predictive of liver hypertrophy/regeneration and immune cell response
Description
Biomarkers predictive of liver hypertrophy/regeneration are evaluated by blood samples and liver biopies
Time Frame
The day of liver preparation, on day 1, day 2 and day 3 after liver preparation and the day of surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boris GUIU, MD
Phone
0467337546
Email
b-guiu@chu-montpellier.fr
Facility Information:
Facility Name
CHU de Montpellier
City
Montpellier
State/Province
Hérault
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boris GUIU, MD
Facility Name
CHU d'Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine Bouvier, MD
Facility Name
Bordeaux University Hospital
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno LAPUYADE
Facility Name
CHU de Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romaric Loffroy, MD
Facility Name
CHU de Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Sengel, MD
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69317
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Agnès Rode, MD
Facility Name
Centre Léon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charles MASTIER, MD
Facility Name
CHU de Nice
City
Nice
ZIP/Postal Code
06202
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Chevallier, MD
Facility Name
APHP - Cochin hospital
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony DOHAN
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
80000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume Vesselle, MD
Facility Name
Hôpital Paul Brousse
City
Villejuif
ZIP/Postal Code
94800
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oriana Ciacio, MD
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry BAERE

12. IPD Sharing Statement

Citations:
PubMed Identifier
32560632
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.
Results Reference
derived

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

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