Evaluation of Treatment Predictors Reflecting Beta-catenin Activation in Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This prospective clinical trial will evaluate PET/CT and genomic liquid biopsy based biomarkers as predictors of clinical therapeutic response to immune-checkpoint inhibitor (ICI) therapy for patients with inoperable hepatocellular carcinoma (HCC). The primary objective of this diagnostic trial is to assess the accuracy of pre-treatment fluorine-18 (18F-) fluorocholine (FCH) PET/CT for predicting a lack of objective response (LOR) after 16 weeks of ICI therapy.

Detailed Description
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This is a prospective open-label single-arm diagnostic clinical trial evaluating fluorine-18 fluorocholine (FCH) PET/CT and cell-free DNA mutation profiling (also referred to as genomic liquid biopsy) as diagnostic tools for predicting therapeutic response in advanced HCC patients receiving immune-checkpoint inhibitor (ICI) therapy. All enrolled subjects will undergo diagnostic testing with FCH PET/CT and genomic liquid biopsy before ICI treatment. A fluorine-18 fluorodeoxyglucose (FDG) PET/CT may also be performed before treatment and after 8 weeks if the pre-treatment FCH PET/CT shows low or heterogeneous tumor uptake. The accuracy of tumor biomarkers based on PET/CT and liquid biopsy for predicting therapeutic outcome and disease progression will be determined using objective clinical endpoints based on the radiographic classification of treatment response by RECIST v1.1 applied to CT or MRI performed after 16 weeks of treatment.

Official Title
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Clinical Trial of Biomarkers for Predicting Immunotherapy Response in Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma Non-resectable

Intervention / Treatment
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* Combination Product: Fluorine-18 fluorocholine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older (no upper limit of age) Hepatocellular carcinoma diagnosis made histologically or radiographically in accordance to National Comprehensive Cancer Network guidelines (3.2019 version or higher) Barcelona Clinic Liver Cancer Stage B or C Has measurable disease defined as at least one tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 on CT/MRI completed within past 6 weeks of eligibility screening Under the care of a licensed medical oncologist Life expectancy > 6 months Deemed eligible for treatment with an immune checkpoint inhibitor agent based on the treating medical oncologist's assessment of previous treatment failure, clinical/performance/virology status, and liver/renal/hematologic function. Child-Pugh score of 7 or less Creatinine clearance ≥ 40 mL/min, measured or calculated using the Cockcroft-Gault formula ALT and AST ≤5x upper limit of normal Total bilirubin ≤3 mg/dL Albumin ≥2.8 g/dL Exclusion Criteria: Weight > 500 lbs (PET/CT limit) Pregnant or lactating female (those of child-bearing potential must be re-screened within 7 days prior to PET/CT imaging) Serious underlying medical condition that would impair patient's ability to tolerate the imaging procedure Concurrent treatment with a non-targeted therapeutic agent. Concurrent enrollment in an ICI-treatment trial and combination ICI treatment are allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: prospective open-label single-arm diagnostic clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tested with Biomarkers<br>For this single arm study, all enrolled subjects will undergo diagnostic testing with FCH PET/CT and genomic liquid biopsy before treatment involving an immune checkpoint inhibitor agent. A fluorine-18 fluorodeoxyglucose (FDG) PET/CT may also be performed before treatment and after 8 weeks if the pre-treatment FCH PET/CT shows low or heterogeneous tumor uptake. | Combination Product: Fluorine-18 fluorocholine<br>* 18F-fluorocholine is a radiopharmaceutical imaging agent intended for use only with positron emission tomography (PET) imaging. PET with in-line computed tomography imaging of the torso will be performed following intravenous administration of a single unit dose of this investigational new drug.<br>* Other names: [18F]fluorocholine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lack of Objective Response | Lack of Objective Response defined after 16 weeks as meeting criteria for either Stable Disease or Progressive Disease based on RECIST v1.1 | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Objective Response defined after 16 weeks as meeting criteria for either Partial Response or Complete Response based on RECIST v1.1 | 16 weeks | 
| Disease Control | Disease Control defined after 16 weeks as meeting criteria for either Partial Response, Complete Response, or Stable Disease based on RECIST v1.1 | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, immunotherapy, positron emission tomography, mutation profiling, liquid biopsy, personalized medicine, diagnostic, fluorocholine, immune checkpoint inhibitor