A Phase III Randomized Study of TACE Plus an Oral Triple-Agent Cocktail Versus TACE Plus First-Line Targeted Immunotherapy in Unresectable Hepatocellular Carcinoma (Cocktail-001)

December 16, 2025 updated by: Jinglin Xia, Shanghai Zhongshan Hospital

A Prospective, Randomized, Open-Label, Multicenter Phase III Trial Evaluating the Efficacy and Safety of Transarterial Chemoembolization Combined With an Oral Triple-Agent Cocktail Regimen Versus Transarterial Chemoembolization Combined With First-Line Targeted Therapy Plus Immunotherapy in Patients With Unresectable Hepatocellular Carcinoma

This is a prospective, multicenter, randomized, open-label phase 3 study evaluating the efficacy and safety of transarterial chemoembolization (TACE) combined with a triple oral cocktail regimen versus TACE combined with targeted therapy plus immunotherapy as first-line treatment for unresectable hepatocellular carcinoma (HCC).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

222

Phase

  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years at the time of enrollment.
  • Diagnosis of hepatocellular carcinoma (HCC) established according to the Chinese National Liver Cancer (CNLC) guidelines, based on imaging findings and/or histopathological confirmation.
  • Not eligible for curative treatment, including surgical resection, local ablation, or liver transplantation.
  • No prior treatment for HCC, including any locoregional or systemic anticancer therapies.
  • Child-Pugh liver function class A or B 7.

Exclusion Criteria:

  • Participants who had another previous or current malignant tumor, except for early-stage cancer with low risk of recurrence or a malignant tumor curatively treated >5 years prior to enrolment with no recurrence
  • Participants who have severe allergy to iodine, and unable to receive TACE
  • Participants who have undergone a liver transplant or allogeneic bone marrow transplantation, or those who are in the waiting list for liver or bone marrow transplantation
  • Participants who had congenital or acquired immune deficiency, such as HIV infection
  • Participants who had a history of gastrointestinal bleeding within 6 months prior to randomization or a definite tendency of gastrointestinal bleeding
  • Participants who had undergone arterial thromboembolism within 6 months prior to randomization or a definite tendency of gastrointestinal bleeding, such as cerebrovascular accident, ≥ CTCAE grade 3 deep vein thrombosis and pulmonary embolism

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A: apatinib + camrelizumab + TACE
Participants will receive apatinib plus camrelizumab on Day 1 of a 21-Day cycle, after every on-demand transarterial chemoembolization procedure.
Drug: Camrelizumab
Camrelizumab: 200mg, iv, Q3W
Device: TACE
TACE if necessary
Drug: Apatinib
Apatinib: 250m, po, QD
Experimental: Arm B: Thalidomide + Capecitabine + Compound cantharides capsule + TACE
Participants assigned to this arm will receive an oral triple-agent regimen consisting of thalidomide, capecitabine, and compound cantharides capsules. The oral regimen will be initiated immediately after the initial transarterial chemoembolization (TACE) procedure and administered continuously thereafter.
Device: TACE
TACE if necessary
Drug: Thalidomide (drug)
Thalidomide：50-75mg, PO, qn;
Drug: Capecitabine
Capecitabine: 500mg, PO, bid
Drug: Compound cantharides capsule
Compound cantharides capsule: 750mg, PO, tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to ~4 years
Overall survival is defined as the time from randomization to death from any cause. OS will be assessed in the intention-to-treat (ITT) population, which includes all randomized participants.
Up to ~4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to ~2 years
Progression-free survival is defined as the time from randomization to the first documented disease progression or death from any cause, whichever occurs first. Tumor progression will be assessed according to the RECICL criteria and the mRECIST criteria by investigators and a blinded independent radiology committee (BIRC) in the ITT population.
Up to ~2 years
Time to Progression (TTP)
Time Frame: Up to ~2 years
Time to progression is defined as the time from randomization to disease progression that is no longer amenable to transarterial chemoembolization (TACE failure or refractoriness), as assessed according to RECICL and mRECIST criteria in the ITT population.
Up to ~2 years
Objective Response Rate (ORR)
Time Frame: Up to ~2 years
Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) after treatment initiation. Tumor response will be assessed according to RECICL and mRECIST criteria by investigators and the BIRC in the ITT population.
Up to ~2 years
Duration of Response (DOR)
Time Frame: Up to ~2 years
Duration of response is defined as the time from the first documented CR or PR to disease progression or death from any cause, whichever occurs first. DOR will be assessed according to RECICL and mRECIST criteria in the ITT population.
Up to ~2 years
Health-Related Quality of Life (HRQoL)
Time Frame: Up to ~2 years
Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Up to ~2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 22, 2025

Primary Completion (Estimated)

June 30, 2030

Study Completion (Estimated)

June 30, 2030

Study Registration Dates

First Submitted

December 16, 2025

First Submitted That Met QC Criteria

December 16, 2025

First Posted (Actual)

December 30, 2025

Study Record Updates

Last Update Posted (Actual)

December 30, 2025

Last Update Submitted That Met QC Criteria

December 16, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2025-745R

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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