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
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT04543617
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 760
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tiragolumab + Atezolizumab Tiragolumab Participants will receive atezolizumab followed by tiragolumab. Arm C: Tiragolumab Placebo + Atezolizumab Placebo Tiragolumab Matching Placebo Participants will receive matching placebos to tiragolumab and atezolizumab. Arm A: Tiragolumab + Atezolizumab Atezolizumab Participants will receive atezolizumab followed by tiragolumab. Arm B: Tiragolumab Placebo + Atezolizumab Atezolizumab Participants will receive atezolizumab followed by tiragolumab matching placebo. Arm B: Tiragolumab Placebo + Atezolizumab Tiragolumab Matching Placebo Participants will receive atezolizumab followed by tiragolumab matching placebo. Arm C: Tiragolumab Placebo + Atezolizumab Placebo Atezolizumab Matching Placebo Participants will receive matching placebos to tiragolumab and atezolizumab.
- Primary Outcome Measures
Name Time Method Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) Arm A vs Arm C: Overall Survival (OS) From randomization to death from any cause (up to approximately 6 years) Arm B vs Arm C: OS From randomization to death from any cause (up to approximately 6 years)
- Secondary Outcome Measures
Name Time Method Arm B vs Arm C: Investigator-Assessed PFS From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) Arm A vs Arm B: Investigator-Assessed PFS From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) Arm A vs Arm B: OS From randomization to death from any cause (up to approximately 6 years) Independent Review Facility (IRF)-Assessed PFS From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) Investigator-Assessed Confirmed Objective Response Rate (ORR) From randomization up to approximately 6 years IRF-Assessed Confirmed ORR From randomization up to approximately 6 years Investigator-Assessed Duration of Objective Response (DOR) 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) IRF-Assessed DOR 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) Percentage of Participants With Adverse Events (AEs) Up to approximately 6 years Serum Concentration of Tiragolumab 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) Serum Concentration of Atezolizumab 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) Percentage of Participants With ADAs to Atezolizumab 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) Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30 Up to approximately 6 years Clinically meaningful changes in physical functioning, role functioning, global health status (GHS)/QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.
Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18 Up to approximately 6 years Clinically meaningful changes in dysphagia as measured by the EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18). EORTC QLQ-OES18 is a modular supplement to the EORTC QLQ-C30 questionnaire for use in participants with esophageal cancer. EORTC QLQ-OES18 consists of 4 multiple-item scale (dysphagia, eating, reflux, and pain) and 6 single items (trouble swallowing saliva, choked when swallowing, dry mouth, trouble with taste, trouble with coughing, and trouble talking) with a recall period of the previous week. Each symptom item is scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores will be linearly transformed to a range of 0 to 100, with higher transformed scores (i.e. closer to 100) reflecting worse symptoms.
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab 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)
Trial Locations
- Locations (166)
Centro Hospitalar do Porto ? Hospital de Santo António
🇵🇹Porto, Portugal
IPO do Porto
🇵🇹Porto, Portugal
Eugene Marais Hospital
🇿🇦Pretoria, South Africa
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, LA Coruna, Spain
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Liaoning cancer Hospital & Institute
🇨🇳Shenyang, China
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Ninewells Hospital
🇬🇧London, United Kingdom
Keio University Hospital
🇯🇵Tokyo, Japan
International Cancer Institute (ICI)
🇰🇪Eldoret, Kenya
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain
Jieyang People's Hospital
🇨🇳Jieyang, China
Sichuan Provincial Cancer Hospital
🇨🇳Chengdu, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Chongqing Sanxia Central Hospital
🇨🇳Chongqing City, China
Chongqing Cancer Hospital
🇨🇳Chongqing, China
HUC
🇵🇹Coimbra, Portugal
Tohoku University Hospital
🇯🇵Miyagi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center
🇨🇳Shenzhen, China
The Affiliated Hospital of Xuzhou Medical College
🇨🇳Xuzhou, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Zhongshan Hospital Xiamen University
🇨🇳Xiamen, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, China
Florida Cancer Specialists - Fort Myers (Broadway)
🇺🇸Fort Myers, Florida, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Great Lakes Cancer Center
🇺🇸Williamsville, New York, United States
Fundacion Favaloro
🇦🇷Buenos Aires, Argentina
Instituto de Investigaciones Metabolicas (Idim)
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Centro Oncologico Riojano Integral (CORI)
🇦🇷La Rioja, Argentina
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
St John of God Hospital
🇦🇺Subiaco, Western Australia, Australia
Tiroler Landeskrankenanstalten Ges.M.B.H.
🇦🇹Innsbruck, Austria
Klinikum Klagenfurt am Wörthersee
🇦🇹Klagenfurt am Wörthersee, Austria
Ordensklinikum Linz Barmherzige Schwestern
🇦🇹Linz, Austria
AKH - Medizinische Universität Wien
🇦🇹Wien, Austria
UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
Anyang Tumor Hosptial
🇨🇳Anyang City, China
Cancer Hospital Chinese Academy of Medical Sciences.
🇨🇳Beijing, China
Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, China
Hunan Cancer Hospital
🇨🇳Changsha City, China
Changzhou Cancer hospital
🇨🇳Changzhou, China
Heping Hospital Affiliated to Changzhi Medical College
🇨🇳Changzhi City, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Shandong Cancer Hospital
🇨🇳Jinan, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, China
The First People's Hospital of Lian Yun Gang
🇨🇳Lianyungang, China
Lishui Central Hospital
🇨🇳Lishui, China
The First Affiliated Hospital to Henan University of Science and Technology
🇨🇳Luoyang, China
Affiliated Drum Tower Hospital of Nanjing University Medical School
🇨🇳Nanjing City, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Hebei Medical University Fourth Hospital
🇨🇳Shijiazhuang, China
Subei People's Hospital of Jiangsu province
🇨🇳Yangzhou City, China
Hopital Claude Huriez
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
Hopital Timone Adultes
🇫🇷Marseille, France
Hopital Du Haut-Leveque
🇫🇷Pessac, France
Chu La Miletrie
🇫🇷Poitiers, France
Hopital Rangueil
🇫🇷Toulouse, France
Med. Fak. d. Otto-von-Guericke-Universität
🇩🇪Magdeburg, Germany
Univ General Hosp Heraklion
🇬🇷Heraklion, Greece
Euromedical General Clinic of Thessaloniki
🇬🇷Thessaloniki, Greece
Pécsi Tudományegyetem
🇭🇺Pécs, Hungary
Szegedi Tudományegyetem
🇭🇺Szeged, Hungary
Hadassah Ein Karem Hospital
🇮🇱Jerusalem, Israel
Rambam Health Corporation
🇮🇱Rambam, Israel
Tel Aviv Sourasky Medical Ctr
🇮🇱Tel Aviv, Israel
Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Campania, Italy
Ospedale Degli Infermi - Faenza
🇮🇹Faenza, Emilia-Romagna, Italy
Asu Fc S. M. Della Misericordia
🇮🇹Udine, Friuli-Venezia Giulia, Italy
Centre Hospitalier Universitaire Mohamed VI
🇲🇦Marrakech, Morocco
Institut National D'oncologie Sidi Med Benabdellah
🇲🇦Rabat, Morocco
Tauranga Hospital, Clinical Trials Unit
🇳🇿Tauranga, New Zealand
Centrum Onkologii
🇵🇱Bydgoszcz, Poland
Centrum Onkologii Ziemi Lubelskiej Im. ?W. Jana Z Dukli
🇵🇱Lublin, Poland
Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
Wielkopolskie Centrum Onkologii im. Marii Sk?odowskiej-Curie
🇵🇱Pozna?, Poland
NIO im Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Dolno?l?skie Centrum Onkologii
🇵🇱Wroc?aw, Poland
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
UniversitätsSpital Zürich
🇨🇭Zürich, Switzerland
Chang Gung Medical Foundation - Kaohsiung;Oncology
🇨🇳Kaohisung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chi-Mei Medical Centre
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Siriraj Hospital
🇹🇭Bangkok, Thailand
Inonu University Faculty of Medicine Turgut Ozal Medical Center
🇹🇷Malatya, Turkey
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Goztepe Prof.Dr. Suleyman Yalcin City Hospital
🇹🇷Kadiköy, Turkey
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Ankara City Hospital
🇹🇷Ankara, Turkey
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
🇹🇷Adana, Turkey
Van Yuzuncu Yil University Hospital
🇹🇷Van, Turkey
Royal Marsden Hospital - Fulham
🇬🇧London, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
CHRU De Brest - Hopital Morvan - Institut De Cancerologie Et D'Hematologie
🇫🇷Brest, France
CHU Dijon Bourgogne Hôpital François Mitterand
🇫🇷Dijon, France
Centre Antoine Lacassagne
🇫🇷Nice, France
European Hospital Georges Pompidou (HEGP)
🇫🇷Paris, France
Universitätsklinikum Essen Klinik f.Strahlentherapie
🇩🇪Essen, Germany
Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie
🇩🇪Essen, Germany
Klinik für Gastroenterologie und Gastrointestinale Onkologie der UMG
🇩🇪Göttingen, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum der Philipps-Universität Marburg
🇩🇪Marburg, Germany
Universitätsklinikum Klinik u.Poliklinik f.Strahlentherapie
🇩🇪Regensburg, Germany
Evgenidio Hospital "Agia Trias"
🇬🇷Athens, Greece
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, Italy
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Kobe University Hospital
🇯🇵Hyogo, Japan
Yokohama City University Medical Center
🇯🇵Kanagawa, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Aga Khan University Hospital
🇰🇪Nairobi, Kenya
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Inselspital Bern, Insel-Gruppe AG
🇨🇭Bern, Switzerland
Vajira Hospital
🇹🇭Bangkok, Thailand
Ankara University Faculty of Medicine Cebeci Hospital
🇹🇷Ankara, Turkey
Osaka University Hospital
🇯🇵Osaka, Japan
Ajou University Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Tatarstan, Russian Federation
City Oncological Hospital
🇷🇺Izhevsk, Udmurtija, Russian Federation
Limited Liability Company "RC Medical"
🇷🇺Novosibirsk, Russian Federation
Regional Oncology Dispensary
🇷🇺Tomsk, Russian Federation
Limpopo Cancer Research Institute
🇿🇦Polokwane, South Africa
Cancercare
🇿🇦Port Elizabeth, South Africa
Saitama Medical University International Medical Center
🇯🇵Saitama, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Univ. Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Centre Hospitalier Universitaire Hassan II
🇲🇦FES, Morocco
Hospital La Fe
🇪🇸Valencia, Spain
Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
🇹🇷Erzurum, Turkey
Municipal Noncommercial Institution Regional Center of Oncology
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
Zhytomyr Regional Oncology Center
🇺🇦Zhytomyr, KIEV Governorate, Ukraine
Vinnytsya Regional Clinical Oncology Dispensary
🇺🇦Vinnytsya, Podolia Governorate, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
Royal Marsden Hospital (Sutton)
🇬🇧Sutton, United Kingdom
Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom