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Phase 3 Study of Tislelizumab Versus Sorafenib in Participants With Unresectable HCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03412773
Recruitment Status : Active, not recruiting
First Posted : January 26, 2018
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Description
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Brief Summary:
This is a Phase 3, randomized, open-label, multicenter, global study designed to compare the efficacy and safety of tislelizumab versus sorafenib as a first-line systemic treatment in participants with unresectable hepatocellular carcinoma. This study also includes a substudy investigating the safety, tolerability, PK, and preliminary efficacy in HCC in Japanese participants. In Japan, preliminary safety and tolerability will be evaluated (Safety Run-In Substudy) before Japanese participants are recruited in this Phase 3 study.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Drug: Tislelizumab Drug: Sorafenib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 674 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RATIONALE-301: A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 Versus Sorafenib as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma
Actual Study Start Date : December 28, 2017
Estimated Primary Completion Date : June 20, 2021
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Sorafenib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: Tislelizumab & Safety Run-In Substudy [Japan Only] Drug: Tislelizumab
200 mg once every 3 weeks (Q3W), intravenous dosing (IV)
Other Name: BGB-A317
Active Comparator: Arm B: Sorafenib Drug: Sorafenib
400 mg twice daily (BID), oral dosing
Other Names:
  • Nexavar
  • BAY43-9006


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From date of randomization up to 4 years, approximately ]
  2. Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  3. Safety Run-In Substudy[Japan only]: Percentage of participants with dose-limiting toxicities (DLT) [Determination of the pivotal Phase 3 dose of tislelizumab in Japanese participants] [ Time Frame: From the date of enrollment up to 28 days [DLT period]. ]
  4. Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  5. Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  6. Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of tislelizumab [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  7. Safety Run-In Substudy[Japan only]:Anti-Drug Antibodies (ADA) against tislelizumab at Cmin [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  8. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  9. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  10. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  11. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately ]
  2. Progression-free survival (PFS) [ Time Frame: From date of randomization up to 4 years, approximately ]
  3. Duration of Response (DOR) [ Time Frame: From first determination of an objective response up to 4 years, approximately ]
  4. Time to Progression (TTP) [ Time Frame: From date of randomization up to 4 years, approximately. ]
  5. Health-Related Quality of Life (HRQoL) [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  6. Disease Control Rate (DCR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
  7. Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
  8. Percentage of participants with adverse events [ Time Frame: From date of screening up to 4 years, approximately. ]
  9. Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately. ]
  10. Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) [ Time Frame: From date of randomization up 4 years, approximately ]
  11. Safety Run-In Substudy[Japan only]: Duration of Response (DOR) [ Time Frame: From date of randomization up 4 years, approximately ]
  12. Safety Run-In Substudy[Japan only]: Overall Survival (OS) [ Time Frame: From date of randomization up 4 years, approximately ]
  13. Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody [ Time Frame: From first dose of study treatment up 4 years, approximately ]
  14. Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  15. Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  16. Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  17. Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Histologically confirmed diagnosis of HCC
  2. Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach
  3. No prior systemic therapy for HCC (with the exception of HCC participants enrolled in the safety run-in substudy [Japan only])
  4. Measurable disease
  5. Child-Pugh score A
  6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1
  7. Adequate organ function

Key Exclusion Criteria:

  1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
  2. Tumor thrombus involving main trunk of portal vein or inferior vena cava
  3. Loco-regional therapy to the liver within 28 days before randomization
  4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
  5. Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment
  6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse
  7. Participant with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization
  8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy
  9. QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03412773


Locations
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Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Yaxi Chen, MD BeiGene
More Information
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Publications of Results:

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03412773    
Other Study ID Numbers: BGB-A317-301
2017-002423-19 ( EudraCT Number )
CTR20170882 ( Registry Identifier: Center for drug evaluation, CFDA )
JapicCTI-194569 ( Registry Identifier: Japic )
First Posted: January 26, 2018    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
Advanced liver cancer
RATIONALE-301
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
 Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action