PEARL Trial: Partial TACE Enhancing Anti-tumor Response With Lenvatinib in Unresectable HCC (Pearl)

This is a single-arm, open-label, phase II clinical trial. Patients with unresectable hepatocellular carcinoma (HCC) who are eligible for lenvatinib treatment will receive partial transarterial chemoembolization (TACE) targeting up to two liver segments containing the largest tumor volume or lesions at risk of rupture, in combination with standard lenvatinib therapy. The partial TACE approach is designed as a liver-function-sparing technique that limits ischemic territory while preserving hepatic reserve.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Procedure: Partial transarterial chemoembolization (TACE)

Detailed Description

Primary objective:

-1-year progression-free survival (PFS) by mRECIST

Secondary objectives:

• 1-year overall survival (OS)
• Objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1 and mRECIST
• Incidence of hepatic decompensation within 30 days after treatment (defined as: bilirubin > 3 mg/dL, new or worsened ascites, or hepatic encephalopathy)
• Duration of response (DOR)

Exploratory Endpoints:

• Depth of response (DpR)
• Immune profile changes from baseline (assessed by multiparametric flow cytometry and single-cell RNA sequencing)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: PO-Ting-Lin; Phone Number: 886975362702; Email: linpoting0101@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Diagnosis of HCC confirmed by histology/cytology or typical imaging features, unsuitable for surgical resection or liver transplantation

• Age ≥ 20 years at the time of signing informed consent
• ECOG performance status 0-1
• BCLC stage B or C (without main portal vein thrombosis)
• Child-Pugh score 5-7 (Class A or B7) within 28 days of registration
• Adequate bone marrow, liver, and renal function
• Blood pressure adequately controlled
• Ability to understand and sign written informed consent

Exclusion Criteria:

Prior systemic therapy for HCC

• Main portal vein thrombosis
• Prior locoregional therapy within 4 weeks
• Uncontrolled hypertension
• Clinically significant cardiovascular disease within 6 months
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Partial TACE Enhancing Anti-tumor Response with Lenvatinib in unresectable HCC; Lenvatinib: Oral administration at 12 mg once daily (body weight ≥ 60 kg) or 8 mg once daily (body weight < 60 kg). Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. Partial TACE: Performed within 4 weeks after starting lenvatinib.

Drug: Lenvatinib; Oral lenvatinib 12 mg once daily for body weight 60 kg or greater, or 8 mg once daily for body weight less than 60 kg. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal.; Procedure: Partial transarterial chemoembolization (TACE); Transarterial chemoembolization targeting up to two liver segments containing the largest tumor volume or lesions at risk of rupture, performed within 4 weeks after starting lenvatinib. This liver-function-sparing approach limits the ischemic territory in order to preserve hepatic reserve.; Other Names: Partial TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year progression-free survival (PFS) by mRECIST	Percentage of participants alive and free of disease progression at 1 year. Progression-free survival is measured from the start date of study treatment to the date of first documented disease progression according to modified RECIST (mRECIST) or death from any cause, whichever occurs first.	1 year after start of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year overall survival (OS)	Percentage of participants alive at 1 year. Overall survival is measured from the start date of study treatment to the date of death from any cause.	1 year after start of study treatment
Objective response rate (ORR) by mRECIST	Percentage of participants with a best overall response of confirmed complete response or partial response, as assessed by modified RECIST (mRECIST). Tumor response is assessed by CT or MRI every 12 weeks from the start of study treatment; a first objective response is confirmed by a second imaging assessment 4 weeks later.	Up to 12 months after start of study treatment
Objective response rate (ORR) by RECIST v1.1	Percentage of participants with a best overall response of confirmed complete response or partial response, as assessed by RECIST version 1.1. Tumor response is assessed by CT or MRI every 12 weeks from the start of study treatment; a first objective response is confirmed by a second imaging assessment 4 weeks later.	Up to 12 months after start of study treatment
Disease control rate (DCR) by mRECIST	Percentage of participants with a best overall response of confirmed complete response, partial response, or stable disease, as assessed by modified RECIST (mRECIST). Tumor response is assessed by CT or MRI every 12 weeks from the start of study treatment.	Up to 12 months after start of study treatment
Disease control rate (DCR) by RECIST v1.1	Percentage of participants with a best overall response of confirmed complete response, partial response, or stable disease, as assessed by RECIST version 1.1. Tumor response is assessed by CT or MRI every 12 weeks from the start of study treatment.	Up to 12 months after start of study treatment
Duration of response (DOR) by mRECIST	Time from the date of first documented objective response (complete or partial response) to the date of first documented disease progression, as assessed by modified RECIST (mRECIST). Reported in months.	Up to 12 months after start of study treatment
Incidence of hepatic decompensation	Percentage of participants with hepatic decompensation within 30 days after treatment. Hepatic decompensation is defined as any of the following: total bilirubin greater than 3 mg/dL, new or worsened ascites, or hepatic encephalopathy.	Within 30 days after treatment
Incidence of treatment-emergent adverse events	Number of participants with treatment-emergent adverse events and serious adverse events, graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From first dose of study treatment up to 30 days after the last dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depth of response (maximum percentage reduction from baseline in the sum of viable target lesion diameters)	Maximum percentage reduction from baseline in the sum of viable target lesion diameters, as assessed by modified RECIST (mRECIST). Reported as percentage change from baseline.	Up to 12 months after start of study treatment
Change from baseline in immune cell subset frequencies assessed by multiparametric flow cytometry	Change from baseline in the frequencies of peripheral blood immune cell subsets measured by multiparametric flow cytometry, including CD4+ and CD8+ T cells, regulatory T cells, natural killer cells, mucosal-associated invariant T cells, and myeloid populations, together with the activation and exhaustion markers PD-1, TIM-3, HLA-DR, and CD38. Reported as percentage of live cells.	Baseline, within 24 hours before TACE, within 48 hours after TACE, Week 12, and Week 24
Change from baseline in immune cell composition assessed by single-cell RNA sequencing	Change from baseline in immune cell composition measured by single-cell RNA sequencing of peripheral blood mononuclear cells and tissue samples, reported as percentage of sequenced cells assigned to each annotated immune cell cluster.	Baseline, within 24 hours before TACE, within 48 hours after TACE, Week 12, and Week 24

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: July 25, 2026
• First Submitted That Met QC Criteria: September 14, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: HCC; TACE; lenvatinib; Liver tumor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; lenvatinib
• Other Study ID Numbers: 202600872A3; LHYY001 (Other Grant/Funding Number: Lin Huang Yueh-Ying Medical Foundation)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No