TACE Plus Sorafenib Versus TACE Alone for Recurrent Intermediate Hepatocellular Carcinoma (TREAT)

TRansarterial ChEmoembolization Plus SorAfenib Versus Transarterial Chemoembolization Alone for Recurrent Intermediate Hepatocellular Carcinoma: A Phase 3, Open Label, Multicenter, Randomized Controlled Trial

The study is a multicenter phase III randomized trial. The purpose is to investigate both the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib versus TACE alone for recurrent intermediate hepatocellular carcinoma patients.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Sorafenib; Transarterial Chemoembolization
• Intervention / Treatment: Combination product: TACE+sorafenib; Procedure: TACE

Detailed Description

The trial will recruit 162 patients with recurrent intermediate HCC, and they will be randomized (1:1) into two groups (TACE+sorafenib group, TACE group). Patients in TACE+sorafenib group will receive TACE one day following oral sorafenib (initial dose: 400mg BID). Patients in the TACE group will receive TACE alone.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-75 years;
2. Diagnosed as HCC based on the American Association for the Study of Liver Diseases 2018 Guideline on Liver Cancer Diagnosis;
3. Initial tumor recurrence following curative surgical resection (R0 hepatectomy) (two to three lesions with at least one lesion >3 cm in diameter or more than three lesions of any diameter). Tumor burden ≤ 50% and no distant metastasis and macroscopic vascular invasion;
4. Histologically confirmed microvascular invasion in the specimen slices of surgically removed primary tumor;
5. Eastern Cooperative Oncology Group scoring 0-1;
6. Child-Pugh A class;
7. At least 3 months of life expectancy;
8. Adequate hematologic, hepatic and renal function: absolute neutrophil count ≥ 1.5x10^9/L, platelet ≥ 60 x10^9/L, Hb ≥ 90g/L, albumin ≥ 30g/L, total bilirubin ≤ 1.5 x upper limit of normal (ULN) , ALT < 5×ULN, AST < 5×ULN, alkaline phosphatase < 4×ULN, extended prothrombin time not exceeding 6s of ULN, creatine<1.5×ULN.

Exclusion Criteria:

1. Have lesions which are diffuse or can not be evaluated via imaging. Tumor burden>50%;
2. Have a history of hepatic encephalopathy, refractory ascites, severe esophageal and gastric varices or variceal bleeding and obstructive jaundice;
3. Have contraindications for TACE;
4. Have metastasis in central nervous system;
5. Allergic to intravenous contrast agents;
6. Pregnant or breastfeeding women, or expecting to conceive or father children within two years;
7. Infection of HIV, known syphilis requiring treatment;
8. Have a known history of prior invasive malignancies within 5 years before enrolment;
9. Patients with allotransplantation;
10. Severe dysfunction involving heart, kidney or other organs;
11. Severe active clinical infection which is over grade 2 based on NCI-CTC version 4;
12. Patients with mental disorders which may impact informed consent;
13. Unable to orally take drugs;
14. Participating other clinical drug trials 12 months before enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transarterial chemoembolization combined with sorafenib; The initial dose of sorafenib is 400mg BID and the drug therapy will last till outcome events happen or the trial ends. TACE will start one day following oral sorafenib. Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (doxorubicin 50mg for cTACE or 75mg for dTACE) and embolizing agents (gelatin sponge for cTACE or microsphere for dTACE) into blood vessels that help tumor grow.	Combination product: TACE+sorafenib; The initial dose of sorafenib is 400mg BID and the drug therapy will last till outcome events happen or the trial ends. TACE will start one day following oral sorafenib. Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (doxorubicin 50mg for cTACE or 75mg for dTACE) and embolizing agents (gelatin sponge for cTACE or microsphere for dTACE) into blood vessels that help tumor grow.
Active Comparator: Transarterial chemoembolization alone; Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (oxaliplatin 200mg, raltitrexed 4mg, epirubicin 20mg in cTACE or 70mg in dTACE) and embolizing agents (gelatin sponge for cTACE or microsphere for dTACE) into blood vessels that help tumor grow.	Procedure: TACE; Either conventional TACE (cTACE) or drug-eluting beads TACE (dTACE) is optional. TACE will be performed via injecting chemotherapy drugs (doxorubicin 50mg for cTACE or 75mg for dTACE) and embolizing agents (gelatin sponge for cTACE or microsphere for dTACE) into blood vessels that help tumor grow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Defined as the time from randomization until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive.	2 years
Time To Progression	Defined as the time from randomization until disease progression.	2 years
Objective Response Rate	The ratio of patients with complete response or partial response among all patients.	2 years
Disease Control Rate	The ratio of patients with complete response, partial response or stable disease among all patients.	2 years
Adverse Events	Grade 3 or severer hematological or non-hematological adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).	2 years
Scoring of Quality of Life	Using the third edition of European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ-C30).	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Ming Kuang, PhD, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Chlorotrianisene; Sorafenib
• Other Study ID Numbers: 20190921

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