Targeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma
Targeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma Through Image-guided Locoregional Therapy
VA Office of Research and Development
93 participants
Apr 1, 2026
INTERVENTIONAL
Conditions
Summary
Trans-arterial chemoembolization (TACE) is the most commonly used therapy for patients with unresectable hepatocellular carcinoma (HCC). TACE is a minimally invasive procedure that involves placing a catheter into the artery in the liver that feeds the tumor, administering chemotherapeutics and then blocking the artery with embolics in order to kill tumor cells by depriving them of essential oxygen and nutrients. While TACE has a proven survival benefit, local recurrence is common, and long-term survival rates are poor. Prior studies demonstrate that HCC cells survive the oxygen and nutrient deprivation through autophagy, a process of cellular self-eating, to provide nutrients required for survival. The proposed project will leverage this dependency to develop a novel approach to TACE that integrates autophagy inhibition to improve therapeutic response by increasing tumor cell killing and enhancing anti-tumor immunity.
Eligibility
Inclusion Criteria5
- Male or female, aged 18 years, meeting criteria for diagnosis of BCLC B HCC and referred to undergo TACE
- HCC measuring 3 cm in minimum transverse diameter and meets LI-RADS 5 criteria based on cross-sectional imaging as determined by a board-certified, sub-specialty trained radiologist
- Childs Pugh Turcotte A/B7, Performance Status 0
- Informed of investigational nature of this study with provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria9
- QT prolongation on ECG
- Retinopathy on ophthalmologic examination
- Females who are pregnant or breast feeding at the time of screening will not be eligible for this study
- a serum or urine pregnancy test will be performed in women of child-bearing potential at screening
- Prior LRT or systemic therapy to the target lesion
- Contraindication to contrast enhanced MRI or metallic implant within the liver.
- HCQ allergy, porphyria, uncontrolled psoriasis, and existing retinopathy
- Lesion not amenable to biopsy based on pre-TACE imaging as determined by treating interventional radiologist
- Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study)
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Interventions
Hydroxychloroquine to be administered intra-arterially at time of transarterial embolization as well as orally for 6 weeks following the procedure
Lipiodol is an FDA-approved drug delivered agent and embolic which is administered as standard of care for transarterial embolization for hepatocellular carcinoma. Lipiodol will be administered intra-arterially in both arms at the time of procedure.
Placebo will be administered orally for 6 weeks following the procedure to patients in arm 2
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT05842174