Study of Tislelizumab in Combination With Chemotherapy Compared to Chemotherapy Alone for Participants With Urothelial Carcinoma
- Conditions
- Urothelial Carcinoma
- Interventions
- Registration Number
- NCT03967977
- Lead Sponsor
- BeiGene
- Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to compare the efficacy and safety of tislelizumab + either cisplatin or carboplatin + gemcitabine versus placebo+ either cisplatin or carboplatin + gemcitabine in approximately 420 participants with locally advanced or metastatic urothelial carcinoma who have not received prior systemic therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 420
- Male or female aged 18 to 75 years on the day of signing the Informed Consent Form (ICF)
- Histologically confirmed, inoperable, locally advanced, or metastatic urothelial cancer (UC)
- Must be eligible to receive cisplatin or carboplatin in the investigator's judgment
- Have had no prior systemic chemotherapy for locally advanced or metastatic UC
- Must be able to provide fresh or archival tumor tissues with an associated pathological report.
- Must have evaluable disease (either measurable or non-measurable) as defined per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
- Adequate organ function before randomization:
Key
- Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Any approved anticancer therapy within 28 days before randomization.
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- Participants with uncontrolled hypercalcemia
- Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
- History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases
- A known history of HIV infection.
- Prior allogeneic stem cell transplantation or organ transplantation.
- History of severe hypersensitivity reactions to other monoclonal antibodies. 10．History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tislelizumab in combination with chemotherapy Tislelizumab Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Tislelizumab in combination with chemotherapy Cisplatin Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Tislelizumab in combination with chemotherapy Gemcitabine Hydrochloride Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Tislelizumab in combination with chemotherapy Carboplatin Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Placebo in combination with chemotherapy Cisplatin Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Placebo in combination with chemotherapy Placebo Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Placebo in combination with chemotherapy Gemcitabine Hydrochloride Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles Placebo in combination with chemotherapy Carboplatin Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
- Primary Outcome Measures
Name Time Method Overall survival (OS) in the Intent to Treat (ITT) set From first randomization up to 3.5 years, approximately
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) per RECIST v1.1 in ITT From first randomization up to 3.5 years, approximately the proportion of participants who had Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST v1.1 in the ITT Analysis Set
Progression-free survival (PFS) From first randomization up to 3.5 years, approximately the time from randomization to the first objectively documented PD, or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set
Overall survival rate at 1 and 2 years for each treatment arm From first randomization up to 3.5 years, approximately the proportion of OS participants at 1 year and 2 years from randomization in the ITT Analysis Set
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30) From first randomization up to 3.5 years, approximately 1) to assess overall health status/Quality of Life with 2 questions which are with range from minimum score 1 as worse outcome and maximum score 7 as higher values represent a better 2) to assess quality of life with 28 questions about Physical functioning, emotional functioning, social functioning etc. which are with range from minimum scores 1 representing as better to maximum scores 4 as worse outcome.
Duration of response (DOR) From first randomization up to 3.5 years, approximately the time from the first occurrence of a documented objective response to documented Progressive Disease (PD), or death from any cause, whichever occurs first, as determined by the investigator per RECIST v1.1 in the ITT Analysis Set
Incidence and severity of treatment-emergent adverse events (AEs) From first randomization up to 3.5years, approximately Incidence and severity of treatment-emergent adverse events (AEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)v5.0
Change from baseline in European Quality of Life 5-Dimension, 5-Level version (EQ-5D-5L) From first randomization up to 3.5 years, approximately to assess health status with 1) 5 questions about Mobility, Self-Care, Usual activities, Pain/Discomfort, Anxiety/Depression which are with 5 options. 2) one question about health status at the day of completing the questionnaire with range from minimum score 0 as worse outcome to maximum scores 100 as higher values represent as better.
Trial Locations
- Locations (46)
Chinese Pla General Hospital
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Fujian Medical University
🇨🇳Quanzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Jiangsu Province Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Southwest Hospital
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Fifth Medical Center of Pla General Hospital
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
The Second Affiliated Hospital of Xian Jiaotong University
🇨🇳Xian, Shaanxi, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Huadong Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
🇨🇳Chengdu, Sichuan, China
The Second Affiliated Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
Affiliated Cancer Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
Zhejiang Provincial Peoples Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Ningbo First Hospital
🇨🇳Ningbo, Zhejiang, China
The First Provincial Wenzhou Hospital of Zhejiang
🇨🇳Wenzhou, Zhejiang, China
Keelung Chang Gung Memorial Hospital and Loves Lake Branch
🇨🇳Anle Dist, Taiwan
Taipei Veterans General Hospital
🇨🇳Beitou Dist, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Guishan Dist, Taiwan
National Cheng Kung University Hospital
🇨🇳North Dist, Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist, Taiwan