Clincosm LogoSign in Get a demo

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

Sponsor
BeiGene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03412773
Collaborator
(none)
674
Enrollment
143
Locations
2
Arms
52.1
Anticipated Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
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 :
Dec 28, 2017
Anticipated Primary Completion Date :
May 1, 2022
Anticipated Study Completion Date :
May 1, 2022

Arms and Interventions

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 Names:
  • BGB-A317

    		•
    Active Comparator: Arm B: Sorafenib

    Drug: Sorafenib
    400 mg twice daily (BID), oral dosing
    Other Names:
  • Nexavar
  • BAY43-9006

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [From date of randomization up to 4 years, approximately]

    2. Safety Run-In Substudy[Japan only]: Percentage of participants with adverse events [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] [From the date of enrollment up to 28 days [DLT period].]

    4. Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of Tislelizumab [From first dose of study treatment up to 4 years, approximately.]

    5. Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of tislelizumab [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 [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 [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 [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 [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 [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 [From date of enrollment up to 4 years, approximately.]

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) [From date of randomization up to 4 years, approximately]

    2. Progression-free survival (PFS) [From date of randomization up to 4 years, approximately]

    3. Duration of Response (DOR) [From first determination of an objective response up to 4 years, approximately]

    4. Time to Progression (TTP) [From date of randomization up to 4 years, approximately.]

    5. Health-Related Quality of Life (HRQoL) [From date of enrollment up to 4 years, approximately.]

    6. Disease Control Rate (DCR) [From first dose of study treatment up to 4 years, approximately]

    7. Clinical Benefit Rate (CBR) [From first dose of study treatment up to 4 years, approximately]

    8. Percentage of participants with adverse events [From date of screening up to 4 years, approximately.]

    9. Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) [From date of randomization up to 4 years, approximately.]

    10. Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) [From date of randomization up 4 years, approximately]

    11. Safety Run-In Substudy[Japan only]: Duration of Response (DOR) [From date of randomization up 4 years, approximately]

    12. Safety Run-In Substudy[Japan only]: Overall Survival (OS) [From date of randomization up 4 years, approximately]

    13. Safety Run-In Substudy[Japan only]: Anti-tislelizumab antibody [From first dose of study treatment up 4 years, approximately]

    14. Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [From date of enrollment up to 4 years, approximately]

    15. Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [From date of enrollment up to 4 years, approximately]

    16. Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [From date of enrollment up to 4 years, approximately]

    17. Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [From date of enrollment up to 4 years, approximately]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Southern California Research Center Coronado California United States 92118
    2 St. Jude Heritage Healthcare Fullerton California United States 92835
    3 University of California - Hematology and Oncology Los Angeles California United States 90095
    4 Chao Family Comprehensive Cancer Center Orange California United States 92868
    5 Inland Empire Liver Foundation Rialto California United States 92377
    6 Ingalls Memorial Hospital Harvey Illinois United States 60426
    7 Healthcare Research Network III, LLC Tinley Park Illinois United States 60487
    8 Ochsner Medical Center (OMC) - New Orleans ACCRU Network Sit New Orleans Louisiana United States 70121-2429
    9 University Medical Center New Orleans New Orleans Louisiana United States 70121
    10 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    11 UMass Memorial Medical Center Worcester Massachusetts United States 01655
    12 Umdnj-Njms Newark New Jersey United States 07103
    13 Northwell Health/Monter Cancer Center Lake Success New York United States 11042
    14 White Plains Hospital Center for Cancer Care - Oncology White Plains New York United States 10601
    15 Precision Cancer Research / Dayton Physicians Network Kettering Ohio United States 45409
    16 Hahnemann University Hospital - Gastroenterology Hepatology Philadelphia Pennsylvania United States 19102
    17 Cancer Treatment Centers of America - Oncology Philadelphia Pennsylvania United States 19124
    18 Vanderbilt University Medical Center (VUMC) Nashville Tennessee United States 37232
    19 The Mays Cancer Center San Antonio Texas United States 78229
    20 The First Affiliated Hospital of Bengbu Medical College Bengbu Anhui China 233004
    21 Anhui Provincial Hospital Hefei Anhui China 230001
    22 The First Affiliated Hospital Of Anhui Medical University Hefei Anhui China 230022
    23 Anhui Medical University - The Second Hospital Hefei Anhui China 230601
    24 Beijing Cancer Hospital Beijing Beijing China 100142
    25 Chinese PLA General Hospital Beijing Beijing China 100853
    26 302 Military Hospital of China Beijing Beijing China
    27 Beijing YouAn Hospital, Capital Medical University Beijing Beijing China
    28 Cancer Hopital Chinese Academy of Medical Sciences Beijing Beijing China
    29 Fujian Medical University Union Hospital Fuzhou Fujian China 350001
    30 Fujian Provincial Cancer Hospital Fuzhou Fujian China 350014
    31 Guangdong General Hospital Guangzhou Guangdong China 510080
    32 Nanfang Hospital Guangzhou Guangdong China 510515
    33 Sun Yat-sen Memorial Hospital , Sun Yat-sen University Guangzhou Guangdong China
    34 The First Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong China
    35 The First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China 530021
    36 Harbin Medical University Cancer Hospital Harbin Heilongjiang China 150081
    37 Henan Cancer Hospital Zhengzhou Henan China 450008
    38 Hubei Cancer Hospital Wuhan Hubei China 400037
    39 Wuhan Union Hospital Wuhan Hubei China 430023
    40 Nanjing Bayi Hospital Nanjing Jiangsu China 210002
    41 Jiangsu Cancer Hospital Nanjing Jiangsu China 210009
    42 The First Affiliated Hospital of Soochow University Suzhou Jiangsu China
    43 The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi China 330006
    44 Jilin Cancer Hospital Changchun Jilin China
    45 The First Hospital of Jilin University Changchun Jilin China
    46 The Affiliated Hospital Of Qingdao University Qingdao Shandong China
    47 Weifang People's Hospital Weifang Shandong China 261000
    48 Shanghai Cancer Hospital of Fudan University Shanghai Shanghai China 200032
    49 Zhongshan Hospital Fudan University Shanghai Shanghai China 200032
    50 The First Affiliated Hospital Of XI'AN Jiaotong University Xian Shanxi China 710061
    51 Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital Sichuan Sichuan China 610072
    52 Zhongnan Hospital of Wuhan University Wuhan Wuhan China 430071
    53 The First Affiliated Hospital of Zhejiang University HangZhou Zhejiang China 310003
    54 Sir Run Run Shaw Hospital, Zhejiang University Hangzhou Zhejiang China 310016
    55 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    56 Peking Union Medical College Hospital Beijing China 100730
    57 The First Affiliated Hospital of Chongqing Medical University Chongqing China
    58 Tianjin Medical University Cancer Institute and Hospital Tianjin China 300060
    59 Fakultni nemocnice Brno Brno Brno-Mesto Czechia 625 00
    60 Fakultni nemocnice Olomouc Olomouc Czechia 779 00
    61 Fakultni nemocnice v Motole Praha 5 Czechia 150 06
    62 CHU Amiens-Hopital Nord - Hépato-Gastroentérologie Somme Amiens France 80054
    63 CHU Cote De Nacre - Hepato-Gastro-Enterologie Et N Caen, Cedex 05 Basse-Normandie France 14033
    64 Hôpital Privé des Côtes d'Armor - Service oncologie Plérin Bretagne France 22190
    65 Hopital Robert DEBRE, CHU Reims Reims Champagne-Ardenne France 51100
    66 Hospitalier Jean Minjoz Besançon Franche-Comté France 25030
    67 CHU de Grenoble Alpes La Tronche Isere France 38700
    68 Bichat-Beaujon Service Inter Hospitalier De Cancerologie Clichy Cedex Lie-de-France France 92118
    69 Hopital Paul Brousse- Aphp Hopitaux Universitairees Paris Su Villejuif Lie-de-France France 94800
    70 CHU Nantes -hopital hotel Dieu Nantes Loire-Atlantique France 4400
    71 CHU Saint Etienne Rahon Lyon France 42270
    72 CHRU De Lille - Hôpital Claude Huriez Lille Nord France 59037
    73 CHU de Nice - Hôpital de l'Archet II Nice Provence-Alpes-Côte-d'Azur France 3200
    74 CHU Saint Eloi - Pôle Digestif Bretagne Rennes Cedex France
    75 Gustave Roussy - Medical Oncology Villejuif Val-de-Marne France 94805
    76 Hospital of Poitiers Poitiers Vienne France 86021
    77 Krankenhaus Nordwest gGmbH Frankfurt/Main Hessen Germany
    78 Maria Gonzalez-Carmona Bonn Nordrhein-Westfalen Germany 53105
    79 Stefan Pluntke Essen Nordrhein-Westfalen Germany 45136
    80 Universitätsklinikum Düsseldorf Düsseldorf Germany 40225
    81 Medizinische Hochschule Hannover Hannover Germany 30625
    82 Universitätsklinikum Köln Köln Germany 50937
    83 Universitätsklinikum Leipzig AöR Leipzig Germany 4103
    84 Universitätsmedizin Mainz Mainz Germany
    85 IRCCS Saverio De Bellis, AO Gastroenterologia Castellana Grotte Bari Italy 70013
    86 Medical Oncology Feltre Belluno Italy
    87 PO G.Rodolico, AOU Policlinico-Vittorio Emanuele di Catania Catania Catani Italy 95123
    88 Ospedale S.Bortolo, AULSS n.6 Vicenza Vicenza Veneto Italy
    89 Policlinico S.Orsola Malpighi, AOU di Bologna - SSD Malattie Bologna Italy 40138
    90 PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology Cremona Italy
    91 Ospedale Vito Fazzi, ASL Lecce Lecce Italy 73100
    92 AOU Policlinico di Modena Modena Italy
    93 IRCCS Policlinico San Matteo Pavia Italy 27100
    94 Ist. Clinici Scientifici Maugeri - Unità Operativa di Oncologia Pavia Italy 27100
    95 Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS Roma Italy 144
    96 PO Umberto I, AO Ordine Mauriziano Torino Italy
    97 Fujita Health University Hospital Toyoake Aiti [Aichi] Japan 470-1192
    98 Ehime Prefectural Central Hospital - Gastroenterology Matsuyama Ehime Japan 790-0024
    99 Ogaki Municipal Hospital Ogaki Gihu [Gifu] Japan
    100 Hokkaido University Hospital - Gastroenterology Sapporo Hokkaidô [Hokkaido] Japan 060-8648
    101 Kanazawa University Hospital Kanazawa-shi Isikawa [Ishikawa] Japan 9208641
    102 Yokohama City University Medical Center Yokohama Kanagawa Japan 232-0024
    103 Kanagawa Cancer Center Yokohama Kanagawa Japan 241-8515
    104 University Hospital, Kyoto Prefectural Univ of Medicine Kyoto-shi Kyôto [Kyoto] Japan 602-8566
    105 Nagasaki Medical Center Omura Nagasaki Japan 856-8562
    106 Kinki University Hospital, Faculty of Medicine - Hematology & Clinical Oncology Osaka-sayama Osaka Japan 589-8511
    107 Osaka University Hospital Suita Osaka Japan 565-0871
    108 Chiba University Hospital Chiba Tiba [Chiba] Japan 260-8677
    109 Sasaki Foundation Kyoundo Hospital Chiyoda-Ku Tokyo Japan 101-0062
    110 Nihon University Itabashi Hospital - Gastroenterological surgery Itabashi-ku Tôkyô [Tokyo] Japan 173-8610
    111 JRC Medical Center Shibuya-ku Tôkyô [Tokyo] Japan 150-8935
    112 National Center for Global Health and Medicine Shinjuku-ku Tôkyô [Tokyo] Japan 162-8655
    113 Kyushu Medical Center Fukuoka Japan 810-8563
    114 Kumamoto University Hospital Kumamoto Japan 860-8556
    115 Iwate Medical University Hospital Morioka Japan
    116 Hyogo College of Medicine Hospital Nishinomiya-shi Japan 663-8501
    117 Osaka International Cancer Institute Osaka Japan 541-8567
    118 Tottori University Hospital Tottori Japan 683-8504
    119 Wakayama Medical University Wakayama-shi Japan 641-8509
    120 Osaka City General Hospital Osaka Ôsaka [Osaka] Japan 534-0021
    121 Osaka National Hospital Osaka Ôsaka [Osaka] Japan 540-0006
    122 Osaka City University Hospital Osaka Ôsaka [Osaka] Japan 545-8586
    123 Centrum Onkologii Instytut im. M. Sklodowskiej-Curie Warszawa Mazowieckie Poland 02-781
    124 Clinical Research Center Sp. z o.o., Medic-R Sp. K. Poznan Wielkopolskie Poland 60-569
    125 Uniwersyteckie Centrum Kliniczne Gdańsk Poland 80-211
    126 Wojewodzki Szpital Specjalistyczny im. Gromkowskiego we Wroclawiu Wroclaw Poland 51-149
    127 Institut Catalá d´Oncología (I.C.O.) Hospitalet de Llobregat Barcelona Spain
    128 Hospital Universitario Vall d'Hebrón Barcelona Spain 8035
    129 Hospital Universitario Madrid Sanchinarro Centro integral Oncologico Clara Campal (CIOCC) Madrid Spain 28050
    130 Hospital Universitari i Politecnic La Fe Valencia Spain
    131 Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Gastroenterology Kaohsiung Taiwan
    132 Kaohsiung Medical University - Chung-Ho Memorial Hospital Kaohsiung Taiwan
    133 Tri-Service General Hospital - Neihu Branch New Taipei Taiwan
    134 China Medical University Hospital - Transplantology - Taichung Taichung Taiwan
    135 Taichung Veterans General Hospital Taichung Taiwan
    136 National Cheng Kung University Hospital Tainan Taiwan 705
    137 Chi Mei Medical Center - YongKang Tainan Taiwan
    138 Taipei Veterans General Hospital Taipei Taiwan 112
    139 Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital Taipei Taiwan
    140 Queen Elizabeth Hospital - Clinical Reasearch Birmingham United Kingdom B152TH
    141 Royal Free Hospital London NHS Trust London United Kingdom NW3 2QG
    142 King's College Hospital NHS Foundation Trust London United Kingdom SE5 9RS
    143 The Christie NHS Foundation Trust - Oak Road Treatment Centre Withington United Kingdom M20 4BX

    Sponsors and Collaborators

    • BeiGene

    Investigators

    • Study Director: Yaxi Chen, MD, BeiGene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03412773
    Other Study ID Numbers:
    • BGB-A317-301
    • 2017-002423-19
    • CTR20170882
    • JapicCTI-194569
    First Posted:
    Jan 26, 2018
    Last Update Posted:
    Jul 28, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Carcinoma
    Carcinoma, Hepatocellular
    Sorafenib

    Study Results

    No Results Posted as of Jul 28, 2021