A Multicentre Randomised Phase III Trial Comparing Atezolizumab Plus Bevacizumab and Standard Chemotherapy Versus Bevacizumab and Standard Chemotherapy as First-line Treatment for Advanced Malignant Pleural Mesothelioma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 45
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The aim of this clinical trial is to assess the effect of treatment with a monoclonal antibody called atezolizumab in patients diagnosed with a type of lung cancer called malignant pleural mesothelioma. The efficacy (whether the treatment works), safety and tolerability (side effects of treatment) of atezolizumab plus bevacizumab in combination with standard chemotherapy versus bevacizumab in combination with standard chemotherapy will be investigated.
详细描述
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer arising from the mesothelial surface of the pleura. In Europe, the incidence is about 20 per million and is almost always caused by asbestos exposure, with a usual lag time of 30 years between exposure and presentation. Patients diagnosed with advanced MPM have limited treatment options, representing a strict unmet need. Despite decades of clinical research, cytotoxic chemotherapy remains one of the few therapeutic options that has been proven to improve survival in advanced MPM in a randomised controlled trial.
The combination of cisplatin and pemetrexed has become standard first-line therapy worldwide for patients who are not suitable for aggressive surgery or in whom chemotherapy is recommended as part of a multimodality regimen. Carboplatin is often substituted for cisplatin, due to simpler and shorter administration and assumption of a more favourable toxicity profile based on experience in other diseases. Patients with MPM have limited treatment options, representing a strict unmet need.
An antibody is a common type of protein usually made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. The two monoclonal antibodies (atezolizumab and bevacizumab) used in this trial are laboratory-produced antibodies. Atezolizumab is engineered to attach to immune cells to stimulate their activity against cancer cells.
Atezolizumab and bevacizumab are both approved by the European Medicines Agency for the treatment of lung and other cancers. The addition of atezolizumab to bevacizumab plus standard chemotherapy for the treatment of MPM is being investigated in this trial.
All participants will receive 4-6 cycles of standard chemotherapy consisting of carboplatin AUC 5 (area under the plasma concentration versus time curve) plus pemetrexed 500mg/m^2 given intravenously, on day 1 of every 3 week cycle for about 12 to 18 weeks.
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 confirmed advanced malignant pleural mesothelioma (all histological subtypes are eligible)
- •Not amenable for radical surgery based on local standards
- •Evaluable disease or measurable disease as assessed according to the modified response evaluation criteria for solid tumours for mesothelioma (mRECIST) v1.1
- •Availability of tumour tissue for translational research
- •Age >18 years
- •Performance Status 0-1
- •Life expectancy >3 months
- •Adequate haematological, renal and liver function
- •Completed baseline quality of life (QoL) questionnaire
- •Women of childbearing potential and sexually active men must agree to use highly effective contraception
- •Able to understand and give written informed consent and comply with trial procedures
排除标准
- •Prior treatment for malignant pleural mesothelioma. Prior radiotherapy for symptom control is allowed, but the irradiated lesion cannot be used as target lesion. If the patient has another target lesion, the patient is eligible.
- •Treatment with systemic immune-stimulatory agents within 4 weeks or five half-lives of the drug prior to randomisation and during protocol treatment.
- •Treatment with systemic immunosuppressive medications within 2 weeks prior to randomisation and during protocol treatment.
- •Previous allogeneic tissue/solid organ transplant
- •Live vaccines within 4 weeks prior to first dose of protocol treatment
- •Inadequately controlled hypertension
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Significant vascular disease within 6 months prior to randomisation
- •History of haemoptysis
- •Evidence of bleeding diathesis or coagulopathy
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •History of active diverticulitis
- •Previous treatment with atezolizumab and/or bevacizumab or parallel participation in other interventional clinical trial with atezolizumab and/or bevacizumab.
研究组 & 干预措施
Atezolizumab plus bevacizumab plus chemotherapy
Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Pemetrexed (Drug)
Bevacizumab plus chemotherapy
Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Carboplatin (Drug)
Bevacizumab plus chemotherapy
Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Pemetrexed (Drug)
Bevacizumab plus chemotherapy
Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Bevacizumab (Drug)
Atezolizumab plus bevacizumab plus chemotherapy
Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Bevacizumab (Drug)
Atezolizumab plus bevacizumab plus chemotherapy
Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Carboplatin (Drug)
Atezolizumab plus bevacizumab plus chemotherapy
Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From date of randomisation until death from any cause, assessed up to 58 months
Overall survival is defined as the time from the date of randomisation until death from any cause. Data for patients who are not reported as having died at the date of analysis will be censored at the date when they were last known to be alive. Data for patients without post-baseline information will be censored at the date of randomization (plus 1 day).
次要结局
- Objective Response Rate (ORR)(From start of protocol treatment acorss all time-points until end of protocol treatment or, as an alternative approach, until the end of follow-up, assessed up to 58 months)
- Progression-free Survival (PFS) according to the mRECIST v1.1(From date of randomisation until documented progression or death, if progression is not documented, assessed up to 58 months)
- Disease Control (DC) at 24 weeks(24 weeks after protocol treatment start)
- Number of participants with treatment related adverse events according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0(Assessed from the date of informed consent until 90 days after protocol treatment discontinuation. Analysed at 58 months after randomisation of the first patient)
- Time to Treatment Failure (TTF)(From randomisation until discontinuation of protocol treatment for any reason, assessed up to 58 months)
- Duration of Response (DoR)(From date of first documentation of objective response until date of first documented progression/ relapse or death, assessed up to 58 months)