RecruitingInterventionalPhase 2

Clinical Trial of Biomarkers for Predicting Immunotherapy Response in Hepatocellular Carcinoma

NCT ID: NCT04965454Sponsor: Queen's Medical CenterLast updated: 2025-05-01

Summary

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

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.

Arms & interventions

Combination ProductFluorine-18 fluorocholine
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.

Outcome measures

Primary

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
Time frame: 16 weeks

Secondary

Objective Response
Time frame: 16 weeks
Disease Control
Time frame: 16 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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) * Does not qualify for surgical resection or locoregional therapy alone or has disease that has progressed after surgical resection and/or locoregional therapy * 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 9 or less * Creatinine clearance ≥ 40 mL/min, measured or calculated using the Cockcroft-Gault formula * ALT and AST ≤7x upper limit of normal * Total bilirubin ≤4 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.

Study locations (1)

The Queen's Medical Center

Honolulu, Hawaii, 96813

Recruiting

Miles Sato, MS · Contact

808-691-8584 msato@queens.org

Sandi A Kwee, MD · Contact

808-691-5466 skwee@queens.org

Sandi A Kwee, MD · Principal Investigator