Clinical trial NCT06334965: Multi-modal Characterisation of Hepatocellular Carcinoma (HCC) Treated With Targeted Radionuclide Therapy (TRT): Prospective Interventional Multicentre National Cohort
Official title: Multi-modal Characterisation of Hepatocellular Carcinoma (HCC) Treated With Targeted Radionuclide Therapy (TRT): Prospective Interventional Multicentre National Cohort
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Radioembolization
Keywords: transarterial radioembolization
18F Choline PET-MRI
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-03-28
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: OPERANDI project aims to address unmet clinical needs in the current management of advanced-stage HCC treated with TARE by exploring new opportunities provided by imaging-based artificial intelligence (AI) and data augmentation, simultaneous PET-MRI imaging, and novel approaches to increase patient selection and TARE efficacy (genomic profiling, radiopotentiators, and new radionuclides). The research aim to identify predictive and early markers indicative of TARE effectiveness based on a large prospective cohort of HCC patients. This cohort will be used to uncover relevant predictive signatures within the morphological, functional, and molecular imaging data using novel imaging-based AI approaches with a new patient imaging pathway including simultaneous 18F-Choline PET-MRI.

Considering this global objective, the objective of this clinical research protocol is to provide clinical, molecular and imaging data in a prospective standardized study, notably by performing systematic pretherapeutic PET-MRI, in patients with HCC treated with TARE.

Detailed description: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumors, considered the sixth most common cancer and the third major cause of cancer-related death. Its worldwide incidence is expected to increase in the future. Additionally, it shows marked intertumor and intratumor heterogeneity at the microscopic and molecular levels, and there are currently no reliable imaging markers for predicting response to TARE.

TARE is a highly advanced treatment that consists in intra-arterial injection of radioactive microspheres. TARE is already approved for liver metastases and HCC in most countries. So, TARE for HCC, is part of the therapeutic Armamentarium exerting antitumor effects based on radio-biological (DNA damage) and immunological mechanisms. TARE using most currently 90Yttrium-labeled microspheres has proven its non-inferiority with better tolerance and better tumor response in comparison with systemic treatments in patients with HCC.

While highly promising, patient stratification and early identification of responders are currently insufficient due to the lack of pertinent imaging biomarkers, either non-invasive or invasive. Furthermore, prior therapy-induced DNA damages may lead to tumor resistance, therefore reducing TARE efficacy. Hence, the absence of a personalized treatment strategy is an unmet need for patients with HCC. This may result in survival disadvantage for non-responders, who could benefit otherwise from early treatment change, with expected more favorable outcomes.

Simultaneous PET-MRI: OPERANDI proposes a completely innovative and holistic approach via PET-MRI guided therapy. The research hypothesis is that simultaneous PET-MRI imaging provides more robust non-invasive predictive biomarkers than classical approach and better correlation between quantification internal of radiation therapy dosimetry and clinical outcomes than PET-CT. This requires technological development of PET-MRI, with most methodological challenges being attenuation correction, reducing the impact of organ motion due to respiration and cardiac motion, and minimizing truncation and susceptibility artifacts.

A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. This new hybrid technology harnesses the strengths of PET and MRI to produce some of the most highly detailed images currently available. MRI scans use a strong (1.5 to 3T for clinical use) magnetic field to produce detailed morphologic images and some sequences provide functioning information (such as diffusion-weighted, dynamic contrast-enhanced, MR elastography sequence). PET scans use tracers according to the clinical indications to highlight metabolism changes. In HCC, the most common radiotracers are fluorodeoxyglucose (FDG) or Choline, which detect metabolically active malignant lesions.

OPERANDI project aims to address unmet clinical needs in the current management of HCC treated with TARE by exploring new opportunities provided by imaging-based artificial intelligence (AI) and data augmentation, simultaneous PET-MRI imaging, and novel approaches to increase patient selection and TARE efficacy (genomic profiling, radiopotentiators, and new radionuclides). Investigators aim to identify predictive and early markers indicative of TARE effectiveness based on a large prospective cohort of HCC patients. This cohort will be used to uncover relevant predictive signatures within the morphological, functional, and molecular imaging data using novel imaging-based AI approaches with a new patient imaging pathway including simultaneous PET-MRI.

Considering this global objective, the objective of this clinical research protocol is to provide clinical, molecular and imaging data in a prospective standardized study, notably by performing systematic pretherapeutic and follow-up PET-MRI, in patients with HCC treated with TARE.

Eligibility criteria: Inclusion Criteria:

* Patients with HCC for whom TARE decision was made at the MDT
* Patients ≥ 18 years of age
* Diagnosis of HCC based on imaging (EASL guidelines) and confirmed histologically
* At least one target lesion to be treated by radioembolisation, naïve to any previous treatment
* Child-Pugh Class \< B8
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Life expectancy ≥ 3 months
* Available baseline imaging (multiphasic CT), performed within 6 weeks before the beginning of TARE

Exclusion Criteria:

* Patient with contraindication to MRI
* Patient with contraindication to 18F-choline : potential hypersensitivity to the product or to any excipients
* Non-adequate bone marrow, liver and renal function within 15 days prior to work-up as assessed by the following laboratory tests:

  * Hemoglobin ≤ 8.0 g/Dl
  * Platelet count \< 50,000/ mm3
  * Total bilirubin \> 3 mg/dL (or \> 51 µmol/ L).
  * Prothrombin time ≤ 50%
  * Glomerular Filtration Rate (GFR) \< 35 mL/min/1.73 m2
* Infiltrating tumor more than 70% of the liver
* Prior liver transplantation
* Initial prescription for SIRT and concomitant systemic treatment
* Patient refusal to give written and informed consent
* No affiliation to a social security regimen or CMU
* Patient under State Medical Aid
* Known pregnancy or breastfeeding women
* Patient deprived of freedom, subject under a legal protective measure
* Any significant medical, psychiatric, or surgical condition that is uncontrolled and could endanger the subject's safety or limit adherence to the study's objectives and assessments

Primary outcomes:
measure: Clinical response
timeFrame: 12 months after the day of first administration of TARE
Secondary outcomes:
Other outcomes:
Locations:
city: Clichy
country: France
facility: Service de Médecine Nucléaire, Hôpital Beaujon
city: Clichy
country: France
facility: Beaujon hospital
city: Nantes
country: France
facility: CHU Nantes
city: Nantes
country: France
facility: Service de Médecine Nucléaire, CHU de Nantes
city: Paris
country: France
facility: Service de medecine nucleaire, Hôpital Bichat
Study officials:
affiliation: Nantes University Hospital
name: Catherine ANSQUER, Dr
role: PRINCIPAL_INVESTIGATOR
References: