A Phase II, Randomized, Double-Blind Placebo-Controlled Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 162
- 试验地点
- 49
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This study will evaluate the efficacy and safety of atezolizumab with bevacizumab in combination with cisplatin and gemcitabine(CisGem), compared with atezolizumab in combination with CisGem, in participants with advanced biliary tract cancer (BTC) who have not received prior systemic therapy. Treatment will consist of a chemotherapy combination phase followed by a cancer immunotherapy (CIT)/placebo phase.
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
- Double (Participant, Investigator)
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
- •Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
- •Documentation of recurrent/metastatic or locally advanced unresectable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
- •Histologically or cytologically confirmed diagnosis of iCCA, eCCA, or GBC
- •No prior systemic therapy for advanced BTC
- •At least one measurable untreated lesion (per RECIST v1.1)
- •Adequate biliary drainage with no evidence of ongoing infection
- •Eastern Cooperative Oncology Group Performance Status of 0 or 1
- •Life expectancy of > 3 months
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
排除标准
- •Recurrent disease <=6 months after curative surgery or <= 6 months after the completion of adjuvant therapy
- •Prior local regional therapy such as radioembolization
- •Combined or mixed hepatocellular/cholangiocarcinoma
- •Clinically significant hepatic encephalopathy within the 12 months prior to Day 1 of Cycle 1
- •National Cancer Institute Common Terminoogy Criteria for Adverse Events Grade >= 2 peripheral neuropathy
- •Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to Day 1 of Cycle 1
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab, cisplatin or gemcitabine
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- •History of malignancy other than BTC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- •Symptomatic, untreated, or actively progressing CNS metastases
- •For patients with lung metastases, if one of the following criteria applies: Large, centrally located pulmonary metastases; Clear tumor infiltration into the thoracic great vessels seen on imaging; Clear cavitation of pulmonary lesions seen on imaging
- •Active tuberculosis
- •Co-infection with HBV and HCV
- •Treatment with systemic immunostimulatory agents or immunosuppressive medication
- •Inadequately controlled arterial hypertension
- •History of hypertensive crisis or hypertensive encephalopathy
- •Significant vascular disease
- •Evidence of bleeding diathesis or significant coagulopathy
- •Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- •Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
- •Preexisting renal impairment, myelosuppression, or hearing impairment
研究组 & 干预措施
Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Atezolizumab (Drug)
Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Bevacizumab (Drug)
Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Cisplatin (Drug)
Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Gemcitabine (Drug)
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Atezolizumab (Drug)
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Placebo (Other)
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Cisplatin (Drug)
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO
Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)
次要结局
- Duration of Response (DOR)(First occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months))
- Overall Survival (OS)(Randomization to death from any cause (up to approximately 23 months))
- Time to Confirmed Deterioration (TTCD)(Randomization to the first clinically meaningful deterioration (up to approximately 14 months))
- Percentage of Participants With at Least One Adverse Event(Treatment start up to approximately 30 months.)
- Incidence of ADAs to Atezolizumab(At pre-defined intervals from administration of study drug up to approximately 14 months)
- Confirmed Objective Response Rate (ORR)(Randomization up to approximately 14 months)
- Disease Control Rate (DCR)(Randomization up to approximately 14 months)
- Prevalence of ADAs to Atezolizumab(Baseline)
- Serum Concentration of Atezolizumab(Pre-Dose on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and Post Dose Day 1 of Cycle 1 (cycle length=21 days))