Back to resultsEfficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Participants With Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sitravatinib
Tislelizumab
sitravatinib-matching placebo
tislelizumab-matching placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, sitravatinib, tislelizumab
Eligibility Criteria
Key Inclusion Criteria:
- Participant with a first diagnosis of HCC must have undergone a curative-intent resection within 4 to 12 weeks before randomization and have a documented histological confirmation of HCC diagnosis and negative surgical margins (R0 resection) of the resected tumor
- Participant must have tumor-free status as assessed by the investigator and have fully recovered from surgical resection before randomization
- Participant must have no extrahepatic HCC
- ECOG Performance Status ≤ 1
- Participant who has undergone surgical resection and is defined as having a high risk of HCC recurrence
Key Exclusion Criteria:
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
- Evidence of residual, recurrent, or metastatic disease of HCC before randomization
- Major macrovascular (gross vascular) invasion of the portal vein (Vp3 or Vp4) or any grade of macrovascular invasion in the hepatic vein or inferior vena cava
- Untreated chronic hepatitis B (HBV) or chronic HBV carriers with HBV DNA ≥ 2000 IU/mL at Screening
- Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Treatment Arm A: sitravatinib + tislelizumab
Treatment Arm B: Placebo + tislelizumab
Treatment Arm C:Sitravatinib + Placebo
Treatment Arm D: Matching Placebo
Arm Description
sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Outcomes
Primary Outcome Measures
Recurrence-free survival (RFS) as assessed by the investigator between Arm A and Arm D
RFS is defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma (HCC) as assessed by the investigator, or death from any cause, whichever occurs first.
Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Secondary Outcome Measures
Arm A and Arm B: Recurrence-free survival (RFS)
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Arm A and Arm C: Recurrence-free survival (RFS)
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Arm A and Arm D: overall survival (OS)
defined as the time from the date of randomization until the date of death due to any cause
Arm B and Arm D: overall survival (OS)
defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm B: overall survival (OS)
defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm C: overall survival (OS)
defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Number of participants with adverse events (AEs)
Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set
Participants Reported Outcome as measured at Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and its hepatocellular carcinoma cancer module QLQ-HCC18
Quality of Life change with treatment. Scale scores are calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05564338
Brief Title
Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Participants With Hepatocellular Carcinoma
Official Title
A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Compare the Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Surgical Resection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Study has voluntarily discontinued due to a change in the company-level development strategy and is not because of any safety concern or the request from any health authority worldwide.
Study Start Date
June 30, 2023 (Anticipated)
Primary Completion Date
April 30, 2027 (Anticipated)
Study Completion Date
April 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the efficacy and safety of sitravatinib plus tislelizumab or placebo plus tislelizumab versus placebo. The study will also compare the recurrence-free survival (RFS) in participants with hepatocellular carcinoma (HCC) who are at high risk of recurrence after surgical resection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
hepatocellular carcinoma, sitravatinib, tislelizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm A: sitravatinib + tislelizumab
Arm Type
Experimental
Arm Description
sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Arm Title
Treatment Arm B: Placebo + tislelizumab
Arm Type
Experimental
Arm Description
sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Arm Title
Treatment Arm C:Sitravatinib + Placebo
Arm Type
Experimental
Arm Description
sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Arm Title
Treatment Arm D: Matching Placebo
Arm Type
Experimental
Arm Description
sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention Type
Drug
Intervention Name(s)
Sitravatinib
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
sitravatinib-matching placebo
Intervention Description
administered orally
Intervention Type
Drug
Intervention Name(s)
tislelizumab-matching placebo
Intervention Description
administered intravenously
Primary Outcome Measure Information:
Title
Recurrence-free survival (RFS) as assessed by the investigator between Arm A and Arm D
Description
RFS is defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma (HCC) as assessed by the investigator, or death from any cause, whichever occurs first.
Time Frame
Up to 2 Years
Title
Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D
Description
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Time Frame
Up to 2 Years
Secondary Outcome Measure Information:
Title
Arm A and Arm B: Recurrence-free survival (RFS)
Description
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Time Frame
Up to 2 Years
Title
Arm A and Arm C: Recurrence-free survival (RFS)
Description
defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first.
Time Frame
Up to 2 Years
Title
Arm A and Arm D: overall survival (OS)
Description
defined as the time from the date of randomization until the date of death due to any cause
Time Frame
Up to 5 Years
Title
Arm B and Arm D: overall survival (OS)
Description
defined as the time from the date of randomization until the date of death due to any cause
Time Frame
Up to 5 Years
Title
Arm A and Arm B: overall survival (OS)
Description
defined as the time from the date of randomization until the date of death due to any cause
Time Frame
Up to 5 Years
Title
Arm A and Arm C: overall survival (OS)
Description
defined as the time from the date of randomization until the date of death due to any cause
Time Frame
Up to 5 Years
Title
Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator
Description
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Time Frame
Up to 2 Years
Title
Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator
Description
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Time Frame
Up to 2 Years
Title
Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator
Description
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Time Frame
Up to 2 Years
Title
Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator
Description
defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Time Frame
Up to 2 Years
Title
Number of participants with adverse events (AEs)
Description
Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set
Time Frame
Up to 5 Years
Title
Participants Reported Outcome as measured at Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and its hepatocellular carcinoma cancer module QLQ-HCC18
Description
Quality of Life change with treatment. Scale scores are calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100
Time Frame
Up to 2 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Participant with a first diagnosis of HCC must have undergone a curative-intent resection within 4 to 12 weeks before randomization and have a documented histological confirmation of HCC diagnosis and negative surgical margins (R0 resection) of the resected tumor
Participant must have tumor-free status as assessed by the investigator and have fully recovered from surgical resection before randomization
Participant must have no extrahepatic HCC
ECOG Performance Status ≤ 1
Participant who has undergone surgical resection and is defined as having a high risk of HCC recurrence
Key Exclusion Criteria:
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
Evidence of residual, recurrent, or metastatic disease of HCC before randomization
Major macrovascular (gross vascular) invasion of the portal vein (Vp3 or Vp4) or any grade of macrovascular invasion in the hepatic vein or inferior vena cava
Untreated chronic hepatitis B (HBV) or chronic HBV carriers with HBV DNA ≥ 2000 IU/mL at Screening
Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding
Note: Other protocol defined Inclusion/Exclusion criteria may apply
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Participants With Hepatocellular Carcinoma
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