Multi-modal Characterisation of Hepatocellular Carcinoma (HCC) Treated With Targeted Radionuclide Therapy (TRT): Prospective Interventional Multicentre National Cohort

Not Applicable

Not yet recruiting

• Conditions: Hepatocellular Carcinoma; Radioembolization
• Interventions: Other: Simultaneous 18F-Choline PET-MRI

• Registration Number: NCT06334965
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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 and follow-up 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 90Y-loaded 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 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.

Study Timeline

• Study First Submitted: 2024-02-05
• Status Verified: 2024-03
• Study Start: 2024-03
• Study First Submitted QC: 2024-03-21
• Last Update Submitted: 2024-03-21
• Study First Posted: 2024-03-28
• Last Update Posted: 2024-03-28
• Primary Completion: 2027-11
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

• Patients with HCC for whom TARE decision was made at the MDT

• Male or female patients ≥ 18 years of age

• Diagnosis of HCC based on imaging (EASL guidelines) and confirmed histologically

• Liver function status Child-Pugh Class < B8

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:

  1. Hemoglobin > 8.0 g/Dl
  2. Platelet count ≥ 50,000/ mm3
  3. Total bilirubin ≤ 3 mg/dL (or ≤ 51 µmol/ L).
  4. Prothrombin time > 50%
  5. Glomerular Filtration Rate (GFR) ≥ 35 mL/min/1.73 m2

• Life expectancy ≥ 3 months

• Available baseline imaging (multiphasic CT), performed within 6 weeks before the beginning of TARE

• Patients who have signed a consent form to participate in the study, obtained prior to the start of any protocol related activities

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Exclusion Criteria

• Patients with contraindication to MRI
• Contraindication to 18F-choline : potential hypersensitivity to the product or to any excipients
• Patient with severe renal insufficiency
• Multilobular infiltrating tumor more than 70% of the liver
• Prior liver transplantation
• Child-Pugh B9 and C
• Previously treated by surgery or chemo embolization
• Absence of written informed consent from the patient under guardianship or trusteeship
• No affiliation to social security (beneficiary or assignee) (as Patient on AME (state medical aid))
• Known pregnancy or breastfeeding women
• For women of childbearing age, positive pregnancy test (blood or urine)
• Person deprived of liberty and / or person under psychiatric care

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PET-MRI	Simultaneous 18F-Choline PET-MRI	PET-MRI added in care pathway

Primary Outcome Measures

Name	Time	Method
Clinical response	12 months after the day of first administration of TARE	Clinical response defined by the PFS as the time measured from the day of first administration of TARE to first progression or death at 12 months, whichever occurs first

Trial Locations

Locations (2)

Beaujon hospital; 🇫🇷 Clichy, France

CHU Nantes; 🇫🇷 Nantes, France