Clinical trial NCT04540211: A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Patients With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Esophageal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-07
Enrollment: 461
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 atezolizumab plus tiragolumab in combination with paclitaxel and cisplatin (PC) compared with atezolizumab matching placebo plus tiragolumab matching placebo plus PC as first-line treatment in participants with unresectable locally advanced, unresectable recurrent, or metastatic esophageal carcinoma (EC). Participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during induction phase:

Arm A: Atezolizumab plus Tiragolumab and PC Arm B: Atezolizumab placebo plus Tiragolumab placebo and PC Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab matching placebo plus tiragolumab matching placebo (Arm B).


Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed EC
* Unresectable locally advanced, unresectable recurrent, or metastatic disease
* Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate hematologic and end-organ function
* Female participants must be willing to avoid pregnancy and refrain from donating eggs during the treatment period and for 90 days after the final dose
* Male participants with partners of childbearing potential must commit to the use of two methods of contraception and must not donate sperm for the study duration and 90 days after the final dose

Key Exclusion Criteria:

* Palliative radiation treatment for EC within 4 weeks prior to initiation of study treatment
* Evidence of complete esophageal obstruction not amenable to treatment
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Active or history of autoimmune disease or immune deficiency or leptomeningeal disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
* Malignancies other than EC within 2 years prior to screening with a negligible risk of metastasis or death adequately treated with expected curative outcome
* Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
* Positive test result for human immunodeficiency virus (HIV)
* Active hepatitis B or hepatitis C
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with any investigational therapy prior to initiation of study treatment
* Poor peripheral venous access
* Prior allogeneic stem cell or solid organ transplantation
* Concurrent participation in another therapeutic clinical trial

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to death from any cause (up to approximately 35 months)
measure: Independent Review Facility (IRF)-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 35 months)
Secondary outcomes:
measure: Investigator-Assessed PFS
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months)
measure: IRF-Assessed Confirmed Objective Response Rate (ORR)
timeFrame: From randomization up to approximately 35 months
measure: Investigator-Assessed Confirmed ORR
timeFrame: From randomization up to approximately 35 months
measure: IRF-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 35 months)
measure: Investigator-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 35 months)
measure: Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning, Role Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30
timeFrame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)
measure: TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18
timeFrame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 35 months
measure: Minimum Serum Concentration (Cmin) of Tiragolumab
timeFrame: Cycle 1 (cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 35 months)
measure: Maximum Serum Concentration (Cmax) of Tiragolumab
timeFrame: Cycle 1 (cycle=21 days), Day 1: predose, 0.5h postdose; Cycles 2, 3, 4, 8, 12, 16: Day 1: predose and at TD visit (up to approximately 35 months)
measure: Cmin of Atezolizumab
timeFrame: Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months)
measure: Cmax of Atezolizumab
timeFrame: Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months)
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
timeFrame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months)
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months)
Other outcomes:
Locations:
city: Anhui
country: China
facility: Anhui Provincial Hospital
city: Anyang City
country: China
facility: Anyang Tumor Hosptial
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Luhe Hospital Capital Medical University
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Chengde City
country: China
facility: Affiliated Hospital of Chengde Medical University
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: Foshan
country: China
facility: The First People's Hospital of Foshan
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
city: Guangdong Province Guangzhou City
country: China
facility: Southern Medical University Nanfang Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: Anhui Province Cancer Hospital
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
city: Huai An
country: China
facility: Huai'an First People's Hospital
city: Huai'an
country: China
facility: The Second People's Hospital of Huai'an
city: Jining
country: China
facility: Affiliated Hopsital of Jining Medical University
city: Lanzhou
country: China
facility: Gansu Province People Hospital
city: Lianyungang
country: China
facility: The First People's Hospital of Lian Yun Gang
city: Linyi City
country: China
facility: Linyishi Cancer Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital to Henan University of Science and Technology
city: Nanjing City
country: China
facility: Jiangsu Province Hospital of Chinese Medicine
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Nantong City
country: China
facility: Nan Tong Tumor Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
city: Shengyang
country: China
facility: Liaoning Provincial Cancer Hospital
city: Suining
country: China
facility: Suining Central Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Weifang
country: China
facility: Weifang People's 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: Wuxi City
country: China
facility: Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital )
city: Xi'an
country: China
facility: The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Yangzhou City
country: China
facility: Northern Jangsu People's Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang 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: Kaohisung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: