Clinical trial NCT03430843: A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
Official title: A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
Keywords: Unresectable
metastatic
second-line
squamous
esophagus
chemotherapy
paclitaxel
docetaxel
irinotecan
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-02-13
Enrollment: 512
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 was to evaluate the efficacy and safety of tislelizumab as second line treatment in participants with advanced unresectable/metastatic ESCC that had progressed during or after first line therapy.


Eligibility criteria: Key Inclusion Criteria:

1. Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)
2. Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
3. At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization

Key Exclusion Criteria:

1. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
3. Tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
5. Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
6. Prior malignancy active within the previous 2 years (exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast)
7. Active brain or leptomeningeal metastasis.
8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
9. Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc
10. Known history of Human Immunodeficiency Virus (HIV)
11. Has cardiovascular risk factors
12. Pregnant or breastfeeding woman.

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

Primary outcomes:
measure: Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set
timeFrame: Approximately 2 years and 10 months from date of first randomization
Secondary outcomes:
measure: Overall Survival (OS) in the PDL-1 Positive Analysis Set
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Objective Response Rate (ORR) in the ITT Analysis Set
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Progression-free Survival (PFS) in the ITT Analysis Set
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Duration of Response (DOR) in the ITT Analysis Set
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Duration of Response (DOR) in the PDL-1 Positive Analysis Set.
timeFrame: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
measure: Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set
timeFrame: Baseline to Cycle 6 (21 days per cycle)
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From the first dose date to 30 days after the last dose date; up to approximately 4 years and 11 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Uz Antwerpen
city: Leuven
country: Belgium
facility: University Hospitals Leuven
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: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
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: Xiamen
country: China
facility: The First Affiliated Hospital of 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 Sixth Affiliated Hospital, Sun Yat Sen University
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
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: Huaian
country: China
facility: Huaian Second Peoples Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital Branch South
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Province Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Xian
country: China
facility: The Second Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
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: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Brest
country: France
facility: Chru de Brest Hospital Morvan
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Doubs
country: France
facility: Chu Besancon Hopital Jean Minjoz
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Hopital Prive Jean Mermoz
city: Montpellier
country: France
facility: Icm Val Daurelle
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: Ico Site Rene Gauducheau
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Leipzig
country: Germany
facility: Universitares Krebszentrum Leipzig
city: Mainz
country: Germany
facility: Klinikum Johannes Gutenberg Universitaet Mainz
city: Faenza
country: Italy
facility: Ospedale Di Faenza
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
city: Orbassano
country: Italy
facility: Azienda Ospedaliero Universitaria San Luigi Gonzaga
city: Pisa
country: Italy
facility: Aou Pisana, Stabilimento Di Santa Chiara
city: Torino
country: Italy
facility: Ao Citta Della Salute E Della Scienza Di Torino Presidio O
city: Akitashi
country: Japan
facility: Akita University Hospital
state: Akita
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyamashi
country: Japan
facility: Nho Shikoku Cancer Center
state: Ehime
city: Fukuokashi
country: Japan
facility: Nho Kyushu Cancer Center
state: Fukuoka
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Yokohama
country: Japan
facility: St Marianna University School of Medicine Hospital
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Osakashi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Suitashi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Takatsukishi
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
state: Osaka
city: Kitaadachigun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Suntogun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuoku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Kotoku
country: Japan
facility: Cancer Institute Hospital of Jfcr
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Kyoto
country: Japan
facility: Kyoto University Hospital
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: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi
city: Barcelona
country: Spain
facility: Hospital Del Mar
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 Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Hm Madrid Sanchinarro
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital Liouying
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital East Campus
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Greater Manchester
country: United Kingdom
facility: The Christie Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital Nhs Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute Uk
city: London
country: United Kingdom
facility: St Marys Hospital Imperial College Healthcare Nhs Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital (Mount Vernon Cancer Center)
city: Sutton
country: United Kingdom
facility: Royal Marsden Nhs Foundation Royal Marsden Hospital
Study officials:
References:
citation: Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E; RATIONALE-302 Investigators. Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. J Clin Oncol. 2022 Sep 10;40(26):3065-3076. doi: 10.1200/JCO.21.01926. Epub 2022 Apr 20.
citation: Van Cutsem E, Kato K, Ajani J, Shen L, Xia T, Ding N, Zhan L, Barnes G, Kim SB. Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life. ESMO Open. 2022 Aug;7(4):100517. doi: 10.1016/j.esmoop.2022.100517. Epub 2022 Jul 1.