Local Consolidation After Sintilimab Plus Lenvatinib for Metastatic Liver Cancer

NCT07537946 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: EXACT-EMH-HCC-011
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether comprehensive local consolidative therapy added to continued sintilimab plus lenvatinib improves survival compared with continued sintilimab plus lenvatinib alone in patients with oligo-extrahepatic metastatic hepatocellular carcinoma. All enrolled participants receive induction treatment with sintilimab plus lenvatinib for 4 cycles. Participants who achieve disease control and are confirmed by central multidisciplinary review to be feasible for complete consolidation are randomized in a 1:1 ratio to receive either comprehensive local consolidative therapy followed by continued systemic therapy or continued systemic therapy alone. The primary outcome is overall survival.

Conditions

Hepatocellular Carcinoma (HCC); Metastases

Keywords

Oligometastatic; Hepatocellular Carcinoma; Sintilimab; Lenvatinib; Comprehensive Local Consolidative Therapy; Surgery; Ablation

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as the time from randomization to death from any cause.

  From randomization until death from any cause, assessed up to 60 months

Secondary Outcomes (2)

• Time to Strategy Failure

  From randomization through 60 months

• Time to Widespread Progression

  From randomization through 60 months

Study Arms (2)

Induction Sintilimab Plus Lenvatinib Followed by Comprehensive Local Consolidative Therapy and Conti

EXPERIMENTAL

All enrolled participants receive induction sintilimab plus lenvatinib. Participants who achieve disease control and are confirmed by central multidisciplinary review to be feasible for full-lesion consolidation are randomized to receive comprehensive local consolidative therapy to all residual active lesions within 4 to 8 weeks after randomization, followed by continued sintilimab plus lenvatinib.

Drug: Sintilimab; Drug: Lenvatinib; Procedure: Comprehensive Local Consolidative Therapy

Induction Sintilimab Plus Lenvatinib Followed by Continued Systemic Therapy Alone

ACTIVE COMPARATOR

All enrolled participants receive induction sintilimab plus lenvatinib. Participants who achieve disease control and are confirmed by central multidisciplinary review to be feasible for full-lesion consolidation are randomized to continue sintilimab plus lenvatinib alone without protocol-planned comprehensive local consolidative therapy before RECIST-defined progression.

Drug: Sintilimab; Drug: Lenvatinib

Interventions

Sintilimab DRUG

Sintilimab 200 mg administered as an intravenous infusion every 3 weeks during induction and continued after randomization until disease progression, unacceptable toxicity, withdrawal of consent, investigator decision, or a maximum duration of 24 months, according to protocol.

Induction Sintilimab Plus Lenvatinib Followed by Comprehensive Local Consolidative Therapy and Conti; Induction Sintilimab Plus Lenvatinib Followed by Continued Systemic Therapy Alone

Lenvatinib DRUG

Lenvatinib administered orally once daily during induction and continued after randomization until disease progression or unacceptable toxicity. The recommended dose is 12 mg once daily for participants with body weight greater than or equal to 60 kg and 8 mg once daily for participants with body weight less than 60 kg. Dose interruption, reduction, and discontinuation are managed according to protocol and product labeling.

Induction Sintilimab Plus Lenvatinib Followed by Comprehensive Local Consolidative Therapy and Conti; Induction Sintilimab Plus Lenvatinib Followed by Continued Systemic Therapy Alone

Comprehensive Local Consolidative Therapy PROCEDURE

Protocol-specified comprehensive local consolidative therapy directed at all residual active lesions after induction treatment, including stereotactic body radiotherapy, thermal ablation, surgery, or a combination thereof, performed within 4 to 8 weeks after randomization.

Induction Sintilimab Plus Lenvatinib Followed by Comprehensive Local Consolidative Therapy and Conti

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years
• Hepatocellular carcinoma confirmed by imaging and/or histology according to institutional diagnostic standards
• Advanced or unresectable disease with extrahepatic metastases meeting protocol-defined oligo-extrahepatic metastatic disease criteria: 1 to 5 extrahepatic metastatic lesions and no more than 2 involved extrahepatic organs
• At least 1 measurable lesion according to RECIST version 1.1
• No prior systemic therapy for advanced or metastatic hepatocellular carcinoma
• ECOG performance status 0 to 1
• Child-Pugh class A or stable Child-Pugh B7
• Adequate hematologic, hepatic, renal, and coagulation function according to protocol
• Baseline center multidisciplinary team assessment indicating potential feasibility for complete consolidative intent if disease control is achieved after induction
• Written informed consent and willingness to comply with treatment, follow-up, and protocol-required assessments

You may not qualify if:

• More than 5 extrahepatic metastatic lesions or more than 2 involved extrahepatic organs
• Diffuse peritoneal seeding, leptomeningeal disease, or uncontrolled brain metastases
• Main portal vein trunk invasion, extensive inferior vena cava or right atrial tumor thrombus, or disease considered unlikely to become fully consolidable after induction
• Diffuse intrahepatic disease or liver tumor burden considered unlikely to be controllable with protocol-specified local treatment
• Prior PD-1, PD-L1, CTLA-4, anti-VEGF monoclonal antibody, tyrosine kinase inhibitor, or other systemic antitumor therapy for advanced HCC
• Active autoimmune disease requiring systemic immunosuppression
• Active severe infection, including uncontrolled bacterial or fungal infection, active tuberculosis, or uncontrolled hepatitis B without appropriate antiviral therapy
• Gastrointestinal bleeding within the previous 6 months, or untreated or uncontrolled high-risk gastroesophageal varices
• Uncontrolled hypertension, recent major thrombotic event, myocardial infarction, unstable angina, or stroke
• Active interstitial lung disease or noninfectious pneumonitis requiring systemic treatment
• Severe proteinuria or renal dysfunction considered unsuitable for lenvatinib treatment
• Pregnancy or breastfeeding
• Any condition that, in the investigator's judgment, would make participation unsafe or compromise protocol compliance

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasm Metastasis

Interventions

sintilimab; lenvatinib

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Zhao Huang, M.D

CONTACT

+86 13006378908; huangzhao@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is an open-label trial because local consolidative therapy cannot be masked to participants or treating investigators. However, key imaging-based efficacy assessments are performed using blinded independent central review, and outcome assessment is masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: All enrolled participants receive induction sintilimab plus lenvatinib. Participants with disease control and central multidisciplinary team-confirmed complete consolidative feasibility after induction are randomized in a 1:1 ratio to either comprehensive local consolidative therapy plus continued sintilimab and lenvatinib or continued sintilimab and lenvatinib alone.

Study Record Dates

• First Submitted: April 12, 2026
• First Posted: April 17, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2031
• Study Completion (Estimated): July 30, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

CN (1)