MANDARIN (S6371)
Primary Purpose
Inoperable Hepatocellular Carcinoma
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
TheraSphere™ Yttrium-90 Glass Microspheres
conventional Transarterial Chemoembolization(cTACE)
Sponsored by
About this trial
This is an interventional treatment trial for Inoperable Hepatocellular Carcinoma
Eligibility Criteria
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
Sites / Locations
- Zhongda Hospital Southeast UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TheraSphere™ Yttrium-90 Glass Microspheres
conventional Transarterial Chemoembolization(cTACE)
Arm Description
Outcomes
Primary Outcome Measures
Time to progression (TTP)
Time to progression (TTP) Definition of progression: Progressive Disease (PD) assessment occurs according to mRECIST occurs according to mRECIST
Safety assessed within 60 days post treatment using NCI-CTCAE v5.0
Safety assessed within 60 days post treatment using NCI-CTCAE v5.0
Secondary Outcome Measures
Hepatic time to progression (hTTP) determined by localized mRECIST (within the treated area)
Objective response rate (ORR) of the index lesion according to localized mRECIST (within the treatment area)
Confirmed ORR according to mRECIST
OS (Overall Survival)
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.
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.
Full Information
NCT ID
NCT05016245
First Posted
August 9, 2021
Last Updated
October 9, 2023
Sponsor
Boston Scientific Corporation
1. Study Identification
Unique Protocol Identification Number
NCT05016245
Brief Title
MANDARIN (S6371)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 13, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Scientific Corporation
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the efficacy and safety of TheraSphereTM yttrium [90Y] glass microsphere in the Chinese patients with inoperable hepatocellular carcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inoperable Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TheraSphere™ Yttrium-90 Glass Microspheres
Arm Type
Experimental
Arm Title
conventional Transarterial Chemoembolization(cTACE)
Arm Type
Active Comparator
Intervention Type
Combination Product
Intervention Name(s)
TheraSphere™ Yttrium-90 Glass Microspheres
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
conventional Transarterial Chemoembolization(cTACE)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to progression (TTP)
Description
Time to progression (TTP) Definition of progression: Progressive Disease (PD) assessment occurs according to mRECIST occurs according to mRECIST
Time Frame
through study completion, an average of 18 months
Title
Safety assessed within 60 days post treatment using NCI-CTCAE v5.0
Description
Safety assessed within 60 days post treatment using NCI-CTCAE v5.0
Time Frame
within 60 days post treatment
Secondary Outcome Measure Information:
Title
Hepatic time to progression (hTTP) determined by localized mRECIST (within the treated area)
Time Frame
through study completion, an average of 18 months
Title
Objective response rate (ORR) of the index lesion according to localized mRECIST (within the treatment area)
Time Frame
through study completion, an average of 18 months
Title
Confirmed ORR according to mRECIST
Time Frame
through study completion, an average of 18 months
Title
OS (Overall Survival)
Time Frame
through study completion, an average of 18 months
Title
Safety assessed using NCI-CTCAE v 5.0
Description
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.
Time Frame
through study completion, an average of 18 months
Title
Procedure technical success
Description
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.
Time Frame
immediately after the procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuwei ZHANG
Phone
+86-10-85216440
Email
Yuwei.zhang@bsci.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhiyu ZENG, Dr.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gaojun TENG, Dr.
Organizational Affiliation
Zhongda Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaojun TENG, Dr.
12. IPD Sharing Statement
Plan to Share IPD
No
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MANDARIN (S6371)
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