Targeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma

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 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)

Conditions4

Interventions2

Locations1 site

Browse More Trials