Recruiting

Phase 1

Phase 2

TACE with Autophagy InhibitionTargeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma

Sponsor:

VA Office of Research and Development

Code:

NCT05842174

Conditions

Hepatocellular Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Hydroxychloroquine

Lipiodol

Placebo

Study Details

Brief 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.

Conditions

Hepatocellular Carcinoma

Study ID

NCT05842174

Start date

Apr 1, 2026

Status verified date

Apr, 2026

Completion date

Oct 15, 2030

Anticipated

Primary completion date

Sep 30, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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 Criteria:

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)

Study Design

Enrollment

93 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Transarterial Embolization with Hydroxychloroquine

Intra-arterial hydroxychloroquine in Lipiodol + transarterial embolization followed by oral hydroxychloroquine

placebo comparator: Transarterial Embolization without Hydroxychloquine

Intra-arterial Lipiodol + transarterial embolization followed by oral placebo

Interventions

Hydroxychloroquine

Hydroxychloroquine to be administered intra-arterially at time of transarterial embolization as well as orally for 6 weeks following the procedure

Lipiodol

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

Placebo will be administered orally for 6 weeks following the procedure to patients in arm 2

Primary outcome measure

Local Progression Free Survival [ Time Frame: 6 months following treatment ]

Central Contacts and Locations

Central contacts

Terence P Gade, MD PhD

(215) 823-5800 Terence.Gade@va.gov

Locations

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4551

Contacts

Terence P Gade, MD PhD

(215) 823-5800 Terence.Gade@va.gov

Principal Investigator:

Terence P Gade, MD PhD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Apr 16, 2026

Last verified

Apr, 2026

Keywords

Hepatocellular carcinoma
Transarterial Chemoembolization
Transarterial Embolization
Autophagy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-04-16.