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
- Conditions
- Esophageal Cancer
- Interventions
- Registration Number
- NCT04540211
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 461
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Tiragolumab + PC Atezolizumab Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Atezolizumab + Tiragolumab + PC Tiragolumab Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Placebo + PC Cisplatin Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Placebo + PC Atezolizumab Matching Placebo Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Placebo + PC Tiragolumab Matching Placebo Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Atezolizumab + Tiragolumab + PC Paclitaxel Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Placebo + PC Paclitaxel Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. Atezolizumab + Tiragolumab + PC Cisplatin Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From randomization to death from any cause (up to approximately 35 months) Independent Review Facility (IRF)-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 35 months)
- Secondary Outcome Measures
Name Time Method Investigator-Assessed PFS From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months) IRF-Assessed Confirmed Objective Response Rate (ORR) From randomization up to approximately 35 months Investigator-Assessed Confirmed ORR From randomization up to approximately 35 months IRF-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 35 months) Investigator-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 35 months) 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 From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) 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.
TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18 From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) 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 Adverse Events (AEs) Up to approximately 35 months Minimum Serum Concentration (Cmin) of Tiragolumab 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) Maximum Serum Concentration (Cmax) of Tiragolumab 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) Cmin of Atezolizumab 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) Cmax of Atezolizumab 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) Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab 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) Percentage of Participants With ADAs to Atezolizumab 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)
Trial Locations
- Locations (68)
Nan Tong Tumor Hospital
🇨🇳Nantong City, China
Anhui Provincial Hospital
🇨🇳Anhui, China
Anyang Tumor Hosptial
🇨🇳Anyang City, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Beijing Luhe Hospital Capital Medical University
🇨🇳Beijing, China
the First Hospital of Jilin University
🇨🇳Changchun, China
Jilin Cancer Hospital
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha City, China
Affiliated Hospital of Chengde Medical University
🇨🇳Chengde City, China
Sichuan Provincial Cancer Hospital
🇨🇳Chengdu, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Chongqing Sanxia Central Hospital
🇨🇳Chongqing City, China
The First People's Hospital of Foshan
🇨🇳Foshan, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Fujian Provincial Hospital
🇨🇳Fuzhou, China
Southern Medical University Nanfang Hospital
🇨🇳Guangdong Province Guangzhou City, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Anhui Province Cancer Hospital
🇨🇳Hefei, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Huai'an First People's Hospital
🇨🇳Huai An, China
The Second People's Hospital of Huai'an
🇨🇳Huai'an, China
Affiliated Hopsital of Jining Medical University
🇨🇳Jining, China
Gansu Province People Hospital
🇨🇳Lanzhou, China
The First People's Hospital of Lian Yun Gang
🇨🇳Lianyungang, China
Linyishi Cancer Hospital
🇨🇳Linyi City, China
The First Affiliated Hospital to Henan University of Science and Technology
🇨🇳Luoyang, China
Jiangsu Province Hospital of Chinese Medicine
🇨🇳Nanjing City, China
Jiangsu Cancer Hospital
🇨🇳Nanjing City, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Liaoning Provincial Cancer Hospital
🇨🇳Shengyang, China
Suining Central Hospital
🇨🇳Suining, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Weifang People's Hospital
🇨🇳Weifang, China
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital )
🇨🇳Wuxi City, China
The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)
🇨🇳Xi'an, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
Zhongshan Hospital Xiamen University
🇨🇳Xiamen, China
Xiangyang Central Hospital
🇨🇳Xiangyang, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, China
Xuzhou Central Hospital
🇨🇳Xuzhou, China
Northern Jangsu People's Hospital
🇨🇳Yangzhou City, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hosp
🇭🇰Shatin, Hong Kong
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Chang Gung Medical Foundation - Kaohsiung
🇨🇳Kaohisung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist., Taiwan
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Rajavithi Hospital
🇹🇭Bangkok, Thailand
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Songklanagarind Hospital
🇹🇭Songkhla, Thailand