MANDARIN (S6371)

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

Official Title
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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

Conditions
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Inoperable Hepatocellular Carcinoma

Intervention / Treatment
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* Combination Product: TheraSphere™ Yttrium-90 Glass Microspheres
* Procedure: conventional Transarterial Chemoembolization(cTACE)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TheraSphere™ Yttrium-90 Glass Microspheres<br> | Combination Product: TheraSphere™ Yttrium-90 Glass Microspheres<br>* 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<br>|
| Active Comparator: conventional Transarterial Chemoembolization(cTACE)<br> | Procedure: conventional Transarterial Chemoembolization(cTACE)<br>* 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.<br>|

What is the study measuring?
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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 |