Targeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma

NCT05842174 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ONCC-008-22SIO1CX002542
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

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

Keywords

Hepatocellular carcinoma; Transarterial Chemoembolization; Transarterial Embolization; Autophagy

Outcome Measures

Primary Outcomes (1)

• Local Progression Free Survival

  Local progression free survival will be determined on a per lesion basis based on follow-up cross-sectional imaging and modified response evaluation criteria in solid tumors

  6 months following treatment

Study Arms (2)

Transarterial Embolization with Hydroxychloroquine

EXPERIMENTAL

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

Drug: Hydroxychloroquine; Drug: Lipiodol

Transarterial Embolization without Hydroxychloquine

PLACEBO COMPARATOR

Intra-arterial Lipiodol + transarterial embolization followed by oral placebo

Drug: Lipiodol; Drug: Placebo

Interventions

Lipiodol DRUG

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.

Transarterial Embolization with Hydroxychloroquine; Transarterial Embolization without Hydroxychloquine

Placebo DRUG

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

Transarterial Embolization without Hydroxychloquine

Hydroxychloroquine DRUG

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

Transarterial Embolization with Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

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

Philadelphia, Pennsylvania, 19104-4551, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Hydroxychloroquine; Ethiodized Oil

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Iodized Oil; Plant Oils; Oils; Lipids; Plant Preparations; Biological Products; Complex Mixtures

Study Officials

• Terence P Gade, MD PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Terence P Gade, MD PhD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: May 3, 2023
• Study Start: April 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): October 15, 2030
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)