Clinical trial NCT04543617: A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab With or Without Tiragolumab (Anti-TIGIT Antibody) in Patients With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-10
Enrollment: 760
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 tiragolumab plus atezolizumab compared with placebo in participants with unresectable esophageal squamous cell carcinoma (or those who are unable or unwilling to undergo surgery) and whose cancers have not progressed following definitive concurrent chemoradiotherapy (dCRT). Participants will be randomized in a 1:1:1 ratio to receive either tiragolumab plus atezolizumab (Arm A), tiragolumab matching placebo plus atezolizumab (Arm B), or double placebo (Arm C).


Eligibility criteria: Key Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the esophagus
* Unresectable disease ineligible for curative surgery based on the documented opinion of the qualified medical, surgical or radiation oncologist prior to dCRT and is not expected to undergo tumor resection during the course of the study
* dCRT treatment according to regional oncology guidelines for esophageal cancer
* Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens collected prior to initiation of dCRT
* Adequate hematologic and end-organ function prior to randomization
* Women of childbearing potential must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period, for 5 months after the final dose of atezolizumab/placebo, and for 90 days after the final dose of tiragolumab/placebo, whichever is later
* Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of tiragolumab/placebo.

Key Exclusion Criteria:

* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies
* Any unresolved toxicity of National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 from the prior chemoradiation therapy with the exception of irreversible and manageable hearing loss
* Prior allogeneic stem cell or solid organ transplantation
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
* Malignancies other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Treatment with any other investigational agent, including epidermal growth factor receptor (EGFR) inhibitors, with therapeutic intent for esophageal cancer prior to randomization.

Primary outcomes:
measure: Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Arm A vs Arm C: Overall Survival (OS)
timeFrame: From randomization to death from any cause (up to approximately 6 years)
measure: Arm B vs Arm C: OS
timeFrame: From randomization to death from any cause (up to approximately 6 years)
Secondary outcomes:
measure: Arm B vs Arm C: Investigator-Assessed PFS
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Arm A vs Arm B: Investigator-Assessed PFS
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Arm A vs Arm B: OS
timeFrame: From randomization to death from any cause (up to approximately 6 years)
measure: Independent Review Facility (IRF)-Assessed PFS
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Investigator-Assessed Confirmed Objective Response Rate (ORR)
timeFrame: From randomization up to approximately 6 years
measure: IRF-Assessed Confirmed ORR
timeFrame: From randomization up to approximately 6 years
measure: Investigator-Assessed Duration of Objective Response (DOR)
timeFrame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: IRF-Assessed DOR
timeFrame: From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 6 years
measure: Serum Concentration of Tiragolumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at treatment discontinuation (TD) visit (up to approximately 6 years)
measure: Serum Concentration of Atezolizumab
timeFrame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years)
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
timeFrame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years)
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years)
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (Broadway)
state: Florida
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Williamsville
country: United States
facility: Great Lakes Cancer Center
state: New York
city: Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas (Idim)
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Hospital
state: Western Australia
city: Innsbruck
country: Austria
facility: Tiroler Landeskrankenanstalten Ges.M.B.H.
city: Klagenfurt am Wörthersee
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
city: Linz
country: Austria
facility: Ordensklinikum Linz Barmherzige Schwestern
city: Wien
country: Austria
facility: AKH - Medizinische Universität Wien
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Anyang City
country: China
facility: Anyang Tumor Hosptial
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences.
city: Bengbu
country: China
facility: Affiliated Hospital of Bengbu Medical College
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Changzhi City
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
city: Changzhou
country: China
facility: Changzhou Cancer hospital
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing City
country: China
facility: Chongqing Sanxia Central Hospital
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yet-sen University Cancer Center
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Jieyang
country: China
facility: Jieyang People's Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
city: Lianyungang
country: China
facility: The First People's Hospital of Lian Yun Gang
city: Lishui
country: China
facility: Lishui Central Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital to Henan University of Science and Technology
city: Nanjing City
country: China
facility: Affiliated Drum Tower Hospital of Nanjing University Medical School
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
city: Shenyang
country: China
facility: Liaoning cancer Hospital & Institute
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center
city: Shijiazhuang
country: China
facility: Hebei Medical University Fourth Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan City
country: China
facility: Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
city: Yangzhou City
country: China
facility: Subei People's Hospital of Jiangsu province
city: Brest
country: France
facility: CHRU De Brest - Hopital Morvan - Institut De Cancerologie Et D'Hematologie
city: Dijon
country: France
facility: CHU Dijon Bourgogne Hôpital François Mitterand
city: Lille
country: France
facility: Hopital Claude Huriez
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital Timone Adultes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: European Hospital Georges Pompidou (HEGP)
city: Pessac
country: France
facility: Hopital Du Haut-Leveque
city: Poitiers
country: France
facility: Chu La Miletrie
city: Toulouse
country: France
facility: Hopital Rangueil
city: Essen
country: Germany
facility: Universitätsklinikum Essen Klinik f.Strahlentherapie
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
city: Göttingen
country: Germany
facility: Klinik für Gastroenterologie und Gastrointestinale Onkologie der UMG
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Magdeburg
country: Germany
facility: Med. Fak. d. Otto-von-Guericke-Universität
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg
city: Regensburg
country: Germany
facility: Universitätsklinikum Klinik u.Poliklinik f.Strahlentherapie
city: Athens
country: Greece
facility: Evgenidio Hospital "Agia Trias"
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion
city: Thessaloniki
country: Greece
facility: Euromedical General Clinic of Thessaloniki
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital
city: Rambam
country: Israel
facility: Rambam Health Corporation
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Ctr
city: Napoli
country: Italy
facility: Università degli Studi della Campania Luigi Vanvitelli
state: Campania
city: Faenza
country: Italy
facility: Ospedale Degli Infermi - Faenza
state: Emilia-Romagna
city: Udine
country: Italy
facility: Asu Fc S. M. Della Misericordia
state: Friuli-Venezia Giulia
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Eldoret
country: Kenya
facility: International Cancer Institute (ICI)
city: Nairobi
country: Kenya
facility: Aga Khan University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: FES
country: Morocco
facility: Centre Hospitalier Universitaire Hassan II
city: Marrakech
country: Morocco
facility: Centre Hospitalier Universitaire Mohamed VI
city: Rabat
country: Morocco
facility: Institut National D'oncologie Sidi Med Benabdellah
city: Tauranga
country: New Zealand
facility: Tauranga Hospital, Clinical Trials Unit
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej Im. ?W. Jana Z Dukli
city: Olsztyn
country: Poland
facility: Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii
city: Pozna?
country: Poland
facility: Wielkopolskie Centrum Onkologii im. Marii Sk?odowskiej-Curie
city: Warszawa
country: Poland
facility: NIO im Marii Sklodowskiej-Curie
city: Wroc?aw
country: Poland
facility: Dolno?l?skie Centrum Onkologii
city: Coimbra
country: Portugal
facility: HUC
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto ? Hospital de Santo António
city: Porto
country: Portugal
facility: IPO do Porto
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
state: Sankt Petersburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
state: Tatarstan
city: Izhevsk
country: Russian Federation
facility: City Oncological Hospital
state: Udmurtija
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "RC Medical"
city: Tomsk
country: Russian Federation
facility: Regional Oncology Dispensary
city: Polokwane
country: South Africa
facility: Limpopo Cancer Research Institute
city: Port Elizabeth
country: South Africa
facility: Cancercare
city: Pretoria
country: South Africa
facility: Eugene Marais Hospital
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias
state: Asturias
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital La Fe
city: Bern
country: Switzerland
facility: Inselspital Bern, Insel-Gruppe AG
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Kaohisung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung;Oncology
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Centre
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Adana
country: Turkey
facility: Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine Cebeci Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Erzurum
country: Turkey
facility: Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
city: Kadiköy
country: Turkey
facility: Goztepe Prof.Dr. Suleyman Yalcin City Hospital
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine Turgut Ozal Medical Center
city: Van
country: Turkey
facility: Van Yuzuncu Yil University Hospital
city: Kharkiv
country: Ukraine
facility: Municipal Noncommercial Institution Regional Center of Oncology
state: Kharkiv Governorate
city: Zhytomyr
country: Ukraine
facility: Zhytomyr Regional Oncology Center
state: KIEV Governorate
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Oncology Dispensary
state: Podolia Governorate
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: London
country: United Kingdom
facility: Ninewells Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trial
role: STUDY_DIRECTOR
References: