A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 931
- 试验地点
- 217
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This is a Phase III, global, multicenter, open-label, two-arm, randomized, controlled study designed to evaluate the efficacy and safety of atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer (UBC) who have progressed during or following a platinum-containing regimen. The anticipated time on study treatment is based on continued clinical benefit, i.e., until disease progression or unacceptable toxicity. The target sample size is 931 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra).
- •Representative tumor specimens as specified by the protocol
- •Disease progression during or following treatment with at least one platinum-containing regimen for inoperable, locally advanced or metastatic UBC or disease recurrence
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy greater than or equal to (>/=) 12 weeks
- •Measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end organ function
- •For women of childbearing potential, agreement to refrain from heterosexual intercourse or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, 3 months after the last dose of vinflunine and 6 months from the last dose of paclitaxel or docetaxel.
- •For men, agreement to refrain from heterosexual intercourse or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of vinflunine and 6 months from the last dose of paclitaxel or docetaxel, and agreement to refrain from donating sperm
排除标准
- •Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
- •Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
- •Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- •Leptomeningeal disease
- •Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome, or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer
- •Pregnant and lactating women
- •Significant cardiovascular disease
- •Severe infections within 4 weeks prior to randomization
- •Major surgical procedure other than for diagnosis within 4 weeks prior to randomization
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •History of autoimmune disease
- •Prior allogeneic stem cell or solid organ transplant
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- •Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
- •Administration of a live, attenuated vaccine within 4 weeks prior to randomization
- •Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies
研究组 & 干预措施
Arm A: Atezolizumab
Atezolizumab will be administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants will receive atezolizumab as long as they continue to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
干预措施: Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody (Drug)
Arm B: Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel)
Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Arm B: Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel)
Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm B: Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel)
Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity.
干预措施: Vinflunine (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Between randomization and death due to any cause, up to approximately 25 months after first participant enrolled
OS was defined as time from randomization to death from any cause.
次要结局
- Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1(Up to approximately 25 months after first participant enrolled)
- Percentage of Participants With Post-Baseline Anti-therapeutic Antibodies (ATA) to Atezolizumab(Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days))
- Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Fatigue Symptom Scale(Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days))
- Percentage of Participants With Unconfirmed Objective Response Rate (ORR) as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)(Up to approximately 25 months after first participant enrolled)
- Maximum Observed Serum Atezolizumab Concentration (Cmax)(30 minutes post dose on Day 1 of Cycles 1)
- Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Global Health Status Scale(Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days))
- Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Physical Functioning Scale(Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days))
- Unconfirmed Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1(Up to approximately 25 months after first participant enrolled)
- Percentage of Participants With Adverse Events (AEs)(Up to approximately 46 months after first participant enrolled)
- Minimum Observed Serum Atezolizumab Concentration (Cmin)(Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days))