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)

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: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Camrelizumab; Device: TACE; Drug: Apatinib; Drug: Thalidomide (drug); Drug: Capecitabine; Drug: Compound cantharides capsule

• Study Type: Interventional
• Enrollment (Estimated): 222
• Phase: Phase 2; Phase 3

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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)	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)	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 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)	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)	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)	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

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

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: 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; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Carboxylic Acids; Piperidines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Fluorouracil; Capecitabine; Thalidomide; camrelizumab; apatinib; Pharmaceutical Preparations
• 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