Clinical trial NCT03783442: A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
Official title: A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-12-21
Enrollment: 649
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of tislelizumab as first line treatment in combination with chemotherapy in participants with advanced unresectable/metastatic esophageal squamous cell carcinoma (ESCC).


Eligibility criteria: Key Inclusion Criteria:

1. Pathologically (histologically) confirmed diagnosis of ESCC
2. Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required.

Key Exclusion Criteria:

1. Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
2. Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
3. Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
4. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention)
6. Evidence of complete esophageal obstruction not amenable to treatment
7. Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) \< 83.5 per investigator's choice
8. Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator.
9. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV)

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years and 2 months (as of primary analysis data cut-off date of 28FEB2022)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Objective Response Rate (ORR)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Overall Survival (OS) in the PD-L1 Score ≥ 10% Subgroup
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Duration of Response (DOR)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using European Quality of Life-Core 30 Questionnaire Index (EORTC QLQ-C30)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Esophageal Cancer Specific Module (EORTC QLQ-OES18)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the Generic Health State Instrument European Quality of Life-5 Dimensions (EuroQol 5D EQ-5D-5L)
timeFrame: Approximately 40 months from date of the first participant randomization
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Approximately 40 months from date of the first participant randomization
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital At Yale
state: Connecticut
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Base Hospital
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Brugge
country: Belgium
facility: Az Sint Jan Brugge
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi Site Notre Dame
city: Gent
country: Belgium
facility: UZ GENT
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Liege
country: Belgium
facility: Chc Montlegia
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: The Fifth Medical Center of Chinese Pla General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Quanzhou
country: China
facility: Quanzhou First Affliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Province Traditional Chinese Medical Hospitsal
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital, Sun Yat Sen University
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Nanning
country: China
facility: The Tumor Hospital Affiliated to Guangxi Medical University
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changzhou
country: China
facility: The First Peoples Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital Branch North
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University North Campus (Wuxi Fourth Peoples Hospital )
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Peoples Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Peoples Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Praha
country: Czechia
facility: Fakultni Thomayerova Nemocnice
city: Brest
country: France
facility: Chru de Brest Hospital Morvan
city: Doubs
country: France
facility: Chu Besancon Hopital Jean Minjoz
city: LevalloisPerret
country: France
facility: Hopital Franco Britannique
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon Cedex
country: France
facility: Centre Leon Berard
city: Paris Cedex
country: France
facility: Hopital Saint Antoine Service Dhepato Gastro Enterologie
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Pessac
country: France
facility: Chu Bordeaux Hopital Haut Leveque
city: Poitiers
country: France
facility: Chu de Poitiers Site de La Mileterie
city: SaintHerblain
country: France
facility: Centre de Lutte Contre Le Cancer Institut de Cancerologie de Louest Rene Gauducheau
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Heilbronn
country: Germany
facility: Slk Kliniken Heilbronn Gmbh Klinik Fur Radiologie, Minimalinvasive Therapien Und Nuklearmedizin
city: Leipzig
country: Germany
facility: Universitares Krebszentrum Leipzig
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G Pascale
city: Padova
country: Italy
facility: Iov Istituto Oncologico Veneto Irccs
city: Torrette
country: Italy
facility: Azienda Ospedaliera Universitaria Delle Marche
city: Akitashi
country: Japan
facility: Akita University Hospital
state: Akita
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Fukuokacity
country: Japan
facility: National Hospital Organization Kyushu Medical Center
state: Fukuoka
city: Fukuokashi
country: Japan
facility: Nho Kyushu Cancer Center
state: Fukuoka
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Amagasakishi
country: Japan
facility: Johas Kansai Rosai Hospital
state: Hyogo
city: Yokohamashi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Osakashi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Suitashi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Kitaadachigun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Chuoku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural Univ of Medicine
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Dalseogu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
state: Daegu Gwang'yeogsi
city: Gyeonggido
country: Korea, Republic of
facility: Cha Bundang Medical Center, Cha University
state: Gyeonggi-do
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon Gwang'yeogsi
city: HwasunGun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Smg Snu Boramae Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center Hematology Oncology
state: Seoul Teugbyeolsi
city: Brzozow
country: Poland
facility: Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
city: Koszalin
country: Poland
facility: Szpital Wojewodzki Im Mikoaja Kopernika W Koszalinie
city: Olsztyn
country: Poland
facility: Spzoz Mswia Z Warminsko Mazurskim Centrum Onkologii
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
city: ClujNapoca
country: Romania
facility: Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca
city: ClujNapoca
country: Romania
facility: Medisprof Cancer Center
city: ClujNapoca
country: Romania
facility: Radiotherapy Center Cluj
city: Craiova
country: Romania
facility: Sc Centrul de Oncologie Sf Nectarie Srl
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncological Dispensary
state: Arkhangel'skaya Oblast'
city: Ivanovo
country: Russian Federation
facility: Rbih Ivanovo Regional Oncological Dispensary
state: Ivanovskaya Oblast'
city: Kuzmolovsky
country: Russian Federation
facility: State Budget Healthcare Institution Leningrad Regional Clinical Oncologic Dispensary
state: Leningradskaya Oblast'
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
state: Orenburgskaya Oblast'
city: RostovnaDonu
country: Russian Federation
facility: Rostov State Medical University
state: Rostovskaya Oblast'
city: SaintPetersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
state: Sankt-Peterburg
city: SaintPetersburg
country: Russian Federation
facility: Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Institut Catala Doncologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Chiayi
country: Taiwan
facility: Chiayi Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Tainan
country: Taiwan
facility: Chi Mei Hospital Liouying
city: Greater Manchester
country: United Kingdom
facility: The Christie Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital Nhs Foundation Trust
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Xu J, Kato K, Raymond E, Hubner RA, Shu Y, Pan Y, Park SR, Ping L, Jiang Y, Zhang J, Wu X, Yao Y, Shen L, Kojima T, Gotovkin E, Ishihara R, Wyrwicz L, Van Cutsem E, Jimenez-Fonseca P, Lin CY, Wang L, Shi J, Li L, Yoon HH. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023 May;24(5):483-495. doi: 10.1016/S1470-2045(23)00108-0. Epub 2023 Apr 17.