Multimetabolic 18F-Fluorodeoxyglucose (FDG) and 18F-Fluorocholine (FCH) Positron Emission Tomography (PET) as an Early Predictive Factor of Overall Survival in Patients With Advanced Hepatocellular Carcinoma Treated With Sorafenib (PREMETHEP)

October 9, 2023 updated by: Centre Georges Francois Leclerc

Hepatocellular carcinoma (HCC) is the third cause of death by cancer. For patients with inoperable advanced HCC, systematic therapy with Sorafenib, a multikinase inhibitor that has both antiangiogenic and antiproliferative effect, is the only therapeutic with proven survival benefits. However, the efficacy of Sorafenib remains inconstant with a media overall survival of 10,7 months and a disease control rate only 35 to 43%; moreover, the overall incidence of treatment-related adverse event is 80%. Thus, it appears essential to find an early and accurate way to determine which patients are best responding to therapy in order to avoid the toxicity and cost of ineffective therapy.

Positron Emission Tomography (PET) with 18F-Fluorodeoxyglucose (FDG) has shown limited performance in the setting of HCC because of lack of sensitivity, in particular for well-differentiated tumours. However FDG uptake is related to proliferation rate and is an efficient marker survival following liver transplantation and selective internal radiation therapy. Moreover, the addition of a dynamic first-pass acquisition to the standard static scan provides better characterization of the tumour by adding information on tumour perfusion.

FCH which reflects lipids metabolism and specifically choline kinase activity, has shown promising results for detection of HCC when compared with FDG alone. Moreover, choline activity is related to a kinase pathway in mammalian cells, which is specifically inhibited by Sorafenib. However FCH uptake remains inconstant in HCC, and is related to tumour differentiation, by opposition to FDG. Therefore, several studies have suggested that combined evaluation of tumour glucose and lipid metabolism could play a complementary role for the evaluation of HCC in the setting of detection, staging and to predict recurrence following surgical resection. Thus, the investigator hypothesize that the combination of FDG and FCH may be the most accurate imaging evaluation of HCC.

Thus the aim of the present study is to determine the predictive performance of survival of lipid and glucose metabolism and perfusion changes during Sorafenib therapy in patients with advanced HCC.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Dijon, France, 21000
        • Emilie REDERSTORFF

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient older than 18 years
  • Inoperable (advanced or metastatic) HCC histologically proven, or diagnosed according to the Barcelona criteria, determined to be candidate for Sorafenib therapy
  • Lesion(s) able to be selected as targeted lesion(s) for modified RECIST criteria
  • patient ineligible for curative treatment
  • Child-Pugh liver function (platelet count superior or equal to 60X1 000 000 000per liter; haemoglobin superior or equal to 8,5g/dl
  • Performance status more or equal to 2
  • Able to lie still for 45min for PET/CT scanning
  • Able to understand and willing to signa written informed consent document
  • Affiliated to the French social security social or beneficiary to such a regimen

Exclusion Criteria:

  • Uncontrolled intercurrent illness with short-term life-threatening
  • Pregnant or nursing woman
  • Patient candidate to local/curative therapy of HCC (surgery, radiofrequency, transarterial chemoembolization, other local therapy).
  • History of myocardial infarction less than 6 months before inclusion, uncontrolled hypertension, symptomatic congestive heart failure, anti-arrhythmic therapy (other than beta-blockers or digoxine)
  • History of digestive bleeding less than 30 days before inclusion
  • history of liver transplantation
  • Previous treatment including Sorafenib Uncontrolled diabetes History of allergic reactions attributed to compounds of similar chemical or biologic composition to Fluorocholine, 18F-Fluorodeoxyglucose or Sorafenib
  • Psychiatric illness/social situations that would limit compliance with the study requirements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FDG and FCH PET
Patients will performed a TEP with 2 different radiotracer before treatment is started and 1 month after treatment has been started.
Other: FDG Positron Emission Tomography
Subject will performed Positrons Emission tomography (PET) with 18F-Fluorocholine (FDG) before treatment with Sorafenib is started and 1 month after treatment started.
Other: FCH Positron Emission Tomography
Subject will performed Positrons Emission tomography (PET) with 18F-Fluorocholine (FCH) before treatment with Sorafenib is started and 1 month after treatment started.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vital status
Time Frame: One year after study inclusion
vital status will be death or alive
One year after study inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control
Time Frame: 4 months
Absence of radiologic progression according to modified RECIST criteria
4 months
Questionnaire of quality of life (EORTC QLQ-C30)
Time Frame: 1 year
Questionnaire will be completed by subject at each clinical surveillance visit
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Georges Francois Leclerc

Investigators

  • Study Director: Pierre Fumoleau, Pr, Centre Georges François Leclerc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2017

Primary Completion (Actual)

December 23, 2021

Study Completion (Actual)

December 23, 2021

Study Registration Dates

First Submitted

July 19, 2016

First Submitted That Met QC Criteria

July 27, 2016

First Posted (Estimated)

July 28, 2016

Study Record Updates

Last Update Posted (Actual)

October 11, 2023

Last Update Submitted That Met QC Criteria

October 9, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREMETHEP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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