MANDARIN (S6371)

A Multicentre, Prospective, Open-label, Randomized Controlled Trial on the Efficacy and Safety of TheraSphereTM (Yttrium-90 Glass Microspheres) Compared to Conventional Transarterial Chemoembolization (cTACE) in Chinese Patients With Inoperable Hepatocellular Carcinoma

To evaluate the efficacy and safety of TheraSphereTM yttrium [90Y] glass microsphere in the Chinese patients with inoperable hepatocellular carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Inoperable Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: TheraSphere™ Yttrium-90 Glass Microspheres; Procedure: conventional Transarterial Chemoembolization(cTACE)

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥18 and ≤80 age and provided study consent
• Patients diagnosed with HCC and clinically evaluated as inoperable (as per local practice) or who refuse operation (ablation, hepatectomy and liver transplantation)
• At least one well defined HCC tumor measurable by mRECIST in contrast-enhanced MRI
• China liver cancer staging (CNLC) stage Ib~IIb
• Child-Pugh ≤ B7
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Tumor burden ≤50% of the total liver volume

Exclusion Criteria:

• Presence of extra-hepatic metastases or additional malignancies aside from HCC
• Patients with hepatic artery malformation and unable to intubate hepatic artery
• Patients who are allergic to contrast agents or have renal insufficiency (Serum creatinine>2mg/ml or Creatinine clearance<30mL/min) and are not suitable for injection of contrast agents
• Severe pulmonary insufficiency (FEV1/FVC<50% or FEV1/predicting value<50% or MVV<50L/min)
• AST and ALT >5 times upper limit of normal
• Clinical manifestations of decompensated cirrhosis (Grade2/3 of ascites, gastrointestinal bleeding, hepatic encephalopathy, etc. according to EASL Clinical Practice Guidelines)
• HCC invading biliary tract or causing biliary obstruction
• uncorrectable coagulation dysfunction and severe hemogram abnormality [Prothrombin time (PT)>6 seconds above control or PT-International normalized ratio (INR)>2.5, WBC<3.0x109/L, PLT<50x109/L]
• Infiltrative HCC tumor type
• Bilobar HCC disease
• Any presence of portal vein or hepatic veins or artery invasion
• Occlusion of portal vein completely with less collateral vessels
• Transjugular intrahepatic portosystemic shunt (TIPS) or Hepatic arterioportal fistula
• Patients during pregnancy or lactation
• Prior interventional therapy via hepatic artery or radiotherapy treatment for HCC
• Tc-99m macroaggregated albumin (MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques
• Radiation pneumonitis has been seen in patients receiving doses to the lungs greater than 30 Gy in a single treatment or greater than 50Gy in multiple treatment
• The absorbed dose of lung may exceed 30Gy in preoperative evaluation
• Receive any investigational therapy or anti-tumor therapy within 30 days prior to study enrollment
• Any other reason in which the investigator believes that the patient is unsuitable to participate in this trial

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: TheraSphere™ Yttrium-90 Glass Microspheres	Combination product: TheraSphere™ Yttrium-90 Glass Microspheres; TheraSphere™ Yttrium-90 Glass Microspheres TheraSphere™ is steam sterilized and supplied in 6 standard dose sizes: 3 GBq, 5 GBq, 7 GBq, 10 GBq, 15 GBq, 20 GBq. Custom dose sizes are also available in 0.5 GBq increments between 3 and 20 GBq. TheraSphereTM is supplied with the following accessories: Administration Set Administration Accessory Kit
Active Comparator: conventional Transarterial Chemoembolization(cTACE)	Procedure: conventional Transarterial Chemoembolization(cTACE); conventional Transarterial Chemoembolization(cTACE) is comprised of an anti-neoplastic agent(s) (i.e. cisplatin), lipiodol and embolic agent(s). The choice of agent(s) to be used is per usual local site practice. Chemotherapy agents can be as a single agent or used in combination, as per local practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression (TTP)	Time to progression (TTP) Definition of progression: Progressive Disease (PD) assessment occurs according to mRECIST occurs according to mRECIST	through study completion, an average of 18 months
Safety assessed within 60 days post treatment using NCI-CTCAE v5.0	Safety assessed within 60 days post treatment using NCI-CTCAE v5.0	within 60 days post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic time to progression (hTTP) determined by localized mRECIST (within the treated area)		through study completion, an average of 18 months
Objective response rate (ORR) of the index lesion according to localized mRECIST (within the treatment area)		through study completion, an average of 18 months
Confirmed ORR according to mRECIST		through study completion, an average of 18 months
OS (Overall Survival)		through study completion, an average of 18 months
Safety assessed using NCI-CTCAE v 5.0	Safety assess: to standardize reporting, the National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 5, was used to grade AEs and SAEs. Grades 1, 2, 3, and 4 represented mild, moderate, severe, and life-threatening toxicity, respectively. Grade 5 represented toxicity resulting in death. Descriptive analyses were conducted to assess the safety in each grade and summarized as the number of events and rate per subject.	through study completion, an average of 18 months
Procedure technical success	Procedure technical success is determined successfully if all three items are satisfied at the same time during the operation as follow: Device connected successfully or not;; Microspheres or anti-neoplastic agent(s) (i.e. cisplatin), lipiodol and embolic agent(s). deliver to target area well, or not by device parts;; There was no unplanned release of radiation or leakage of neoplastic agent(s) (i.e. cisplatin), lipiodol and embolic agent(s), or not by device parts.	immediately after the procedure

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Gaojun TENG, Dr., Zhongda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): February 13, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

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
• Other Study ID Numbers: S6371

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: Yes
• product manufactured in and exported from the U.S.: Yes