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

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ClinicalTrials.gov Identifier: NCT03841305
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : April 27, 2020
Sponsor:
Collaborator:
Federation Francophone de Cancerologie Digestive
Information provided by (Responsible Party):
University Hospital, Montpellier

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.

Condition or disease Intervention/treatment Phase
Liver Metastasis Colon Cancer Procedure: Liver preparation before major hepatectomy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 29, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : April 2022

Arm Intervention/treatment
Active Comparator: portal vein embolization
Liver preparation before major hepatectomy : portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.
Procedure: Liver preparation before major hepatectomy
Simultaneous portal and hepatic vein embolization versus Portal vein embolization, also called venous deprivation OR portal vein embolization.

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




Primary Outcome Measures :
  1. 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 ]
    The primary outcomes is to compare the increase in volume of the future remnant liver (FRL)


Secondary Outcome Measures :
  1. Tolerance [ Time Frame: between the day of liver preparation and 90 days after surgery ]
    Toxicities are evaluated according to NCI-CTCAE version 4.03 published 14 June 2010

  2. Post-operative mortality [ Time Frame: 90 days after surgery ]
    Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay

  3. Post-operative morbidity [ Time Frame: 90 days after surgery ]
    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.

  4. Post-hepatectomy liver failure [ Time Frame: between the day of the surgery and 90 days after surgery ]
    Post-hepatectomy liver failure defined according to the "50-50" criteria or peak bilirubin >7mg/dL.

  5. Rate of non-resectability due to insufficient FRL [ Time Frame: between the day of the treatment and the day of the surgery ]
    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

  6. Rate of non-resectability due to tumor progression [ Time Frame: between the day of the treatment and the day of the surgery ]
    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.

  7. Rate of per-operative difficulties [ Time Frame: between the day of the surgery and 90 days after surgery ]
    Rate of per-operative difficulties defined as the percentage of patients for whom per-operative difficulties are encountered by the surgeon

  8. Blood loos, operating time, transfusion [ Time Frame: the day of the surgery ]
    Blood loss are evaluated in mL. Operating time avec evaluated in minutes and transfusion are evaluated by number of packed red blood cells

  9. R0 resection rate [ Time Frame: the day of the surgery ]
    Rate of R0 resection defined as no microscopic tumor residual

  10. R1 resection rate [ Time Frame: the day of the surgery ]
    Rate of R1 resection defined as the percentage of patients resected with margin <1mm

  11. Pre and post-operative liver volumes [ Time Frame: Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery ]
    Pre and post-operative liver volumes will be evaluated through CT or MRI acquisitions by calculating whole liver, tumor and FRL volumes

  12. Recurrence-free survival [ Time Frame: 90 days after surgery ]
    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.

  13. Overall survival [ Time Frame: Between the liver preparation and 90 days after surgery ]
    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.

  14. Evaluation of pre and post-operative liver function [ Time Frame: Baseline, week 1, week 3 then every 2 weeks until surgery or week 7 and 4 weeks after surgery ]
    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

  15. To search for biomarkers predictive of liver hypertrophy/regeneration and immune cell response [ Time Frame: The day of liver preparation, on day 1, day 2 and day 3 after liver preparation and the day of surgery ]
    Biomarkers predictive of liver hypertrophy/regeneration are evaluated by blood samples and liver biopies



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03841305


Contacts
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Contact: Boris GUIU, MD 0467337546 b-guiu@chu-montpellier.fr

Locations
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France
CHU de Montpellier Recruiting
Montpellier, Hérault, France, 34295
Contact: Boris GUIU, MD         
CHU d'Angers Recruiting
Angers, France, 49933
Contact: Antoine Bouvier, MD         
Bordeaux University Hospital Recruiting
Bordeaux, France
Contact: Bruno LAPUYADE         
CHU de Dijon Not yet recruiting
Dijon, France, 21079
Contact: Romaric Loffroy, MD         
CHU de Grenoble Not yet recruiting
Grenoble, France, 38043
Contact: Christian Sengel, MD         
Hospices Civils de Lyon Recruiting
Lyon, France, 69317
Contact: Agnès Rode, MD         
Centre Léon Berard Not yet recruiting
Lyon, France, 69373
Contact: Charles MASTIER, MD         
CHU de Nice Recruiting
Nice, France, 06202
Contact: Patrick Chevallier, MD         
APHP - Cochin hospital Recruiting
Paris, France
Contact: Anthony DOHAN         
CHU de Poitiers Not yet recruiting
Poitiers, France, 80000
Contact: Guillaume Vesselle, MD         
Hôpital Paul Brousse Not yet recruiting
Villejuif, France, 94800
Contact: Oriana Ciacio, MD         
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Thierry BAERE         
Sponsors and Collaborators
University Hospital, Montpellier
Federation Francophone de Cancerologie Digestive
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT03841305    
Other Study ID Numbers: RECHMPL18_0025
UF 7595 ( Other Identifier: UH Montpellier )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: April 27, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Montpellier:
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
Additional relevant MeSH terms:
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Neoplasm Metastasis
Hypertrophy
Neoplastic Processes
Neoplasms
Pathologic Processes
Pathological Conditions, Anatomical
Liver Extracts
Hematinics