Targeting autophagy to improve TACE outcomes in hepatocellular carcinoma
Targeting Ischemia-Induced Autophagy Dependence in Hepatocellular Carcinoma Through Image-guided Locoregional Therapy
This trial will test whether giving hydroxychloroquine with transarterial chemoembolization (TACE) for people with unresectable hepatocellular carcinoma increases tumor cell killing and anti-tumor immune response.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 93 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | VA Office of Research and Development Federal |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Philadelphia, Pennsylvania) |
| Trial ID | NCT05842174 on ClinicalTrials.gov |
What this trial studies
This Phase 1/2 interventional trial adds the autophagy inhibitor hydroxychloroquine to a standard TACE/TAE procedure using lipiodol, with a placebo control arm, to exploit ischemia-induced autophagy dependence in HCC. Eligible patients are adults with BCLC B HCC, a LI-RADS 5 lesion ≥3 cm, Child-Pugh A/B7, and ECOG performance status 0 who are referred for TACE. The protocol builds on preclinical and preliminary clinical observations that HCC cells survive TACE-induced ischemia via enhanced autophagy and become dependent on that pathway. Investigators will measure tumor response, safety (including cardiologic and ophthalmologic monitoring), and signals of enhanced anti-tumor immunity after combining HCQ with TACE.
Who should consider this trial
Good fit: Ideal candidates are adults (≥18) with BCLC B HCC who have a LI-RADS 5 lesion at least 3 cm, Child-Pugh A or B7 liver function, ECOG 0, and are being referred for TACE and can provide informed consent.
Not a fit: Patients with QT prolongation, ophthalmologic retinopathy, pregnancy or breastfeeding, prior local or systemic therapy to the target lesion, or contraindications to contrast-enhanced MRI or the study procedures are unlikely to benefit or are excluded.
Why it matters
Potential benefit: If successful, adding hydroxychloroquine to TACE could increase tumor cell death and improve local control and longer-term outcomes for patients with unresectable HCC.
How similar studies have performed: Preclinical and early clinical data show HCC uses autophagy to survive ischemia and hydroxychloroquine has been tested as an autophagy inhibitor in other cancers, but combining HCQ specifically with TACE for HCC is novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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)
Where this trial is running
Philadelphia, Pennsylvania
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Principal investigator: Terence P Gade, MD PhD — Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
- Study coordinator: Terence P Gade, MD PhD
- Email: Terence.Gade@va.gov
- Phone: (215) 823-5800
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.