Mesothelioma Stratified Therapy (MiST): A Stratified Multi-arm Phase IIa Clinical Trial to Enable Accelerated Evaluation of Targeted Therapies for Relapsed Malignant Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
研究概览
简要总结
MiST is a British Lung Foundation funded, University of Leicester Study, a multi-arm stratified therapy based clinical trial for patients with relapsed mesothelioma.
The goal of MiST is to enable acceleration of novel, effective personalised therapy as a basis for improving survival outcomes for patients with mesothelioma.
详细描述
Stage 1 - molecular pre-screening:
The MiST Master protocol describes the identification of patients, biomarker testing and analysis. Patients with relapsed mesothelioma will be offered to consent for molecular panel testing of their diagnostic tumour block for predictive biomarkers. The results of this assessment will be used to classify patients into one of several possible molecularly defined treatment arms. Patients will therefore be offered a specific study treatment determined by their molecular profile. Patients, who exhibit positive testing in more than one biomarker, will potentially be eligible to subsequently be treated on a different treatment protocol upon disease progression or treatment failure.
Stage 2 - Treatment:
The MiST treatment protocol will be specific to the treatment allocated to the patient - based on the results of their biomarker testing in stage 1.
Specific agent(s) will be detailed separately in each of the separate treatment protocols.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •FOR PRE-SCREENING
- •Histologically confirmed MM with an available biopsy for research purposes
- •Male or female patients aged ≥18 years.
- •Expected survival of ≥12 weeks or greater
- •ECOG PS 0-1
- •CT scan chest, abdomen (and pelvis if applicable) confirming disease progression.
- •Patients must have received at least one prior line of therapy to include a platinum doublet first-line chemotherapy (within or outside of another clinical trial)
- •Willing to consent for molecular screening of archived tumour block (PIS1 & CF1)
排除标准
- •FOR PRE-SCREENING
- •Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission, patients with a diagnosis of basal cell carcinoma of the skin or superficial bladder cancer.
- •Uncontrolled CNS disease. Asymptomatic brain metastases are allowed if previously treated with radiotherapy >28 days prior to starting the investigational agent.
- •New York Heart Association Class II or greater congestive heart failure.
- •Patients with severe hepatic insufficiency or severe renal impairment.
- •Patients requiring long term oxygen therapy.
- •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
- •Each individual MiST drug protocol contains the eligibility criteria specific to the treatment allocated to the patient.
研究组 & 干预措施
MiST 5 Dostarlimab and Niraparib
Platinum sensitive mesothelioma: Niraparib 200-300mg daily every 21 days; Dostarlimab 500mg on day 1 of each 21 day cycle for 4 cycles, then 1000mg on day 1 of each 42 day cycle.
干预措施: Dostarlimab and Niraparib (Drug)
MiST4 Atezolizumab & Bevacizumab
PDL1 expression positive mesothelioma: Atezolizumab 1200 milligrams via intravenous nfusion; Bevacizumab 15 milligrams per kilogram via IV infusion both on Days 1 every 21-days.
干预措施: Atezolizumab & Bevacizumab (Drug)
MiST2 Abemaciclib
p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.
干预措施: Abemaciclib (Drug)
MiST3 Pembrolizumab & Bemcentinib
No specific biomarker requirement: Pembrolizumab 200mg IV infusion on Day 1 only:
Bemcentinib loading dose of 400mg on days 1-3, on day 4 on-wards 200mg daily every 21-days.
干预措施: pembrolizumab & bemcentinib (Drug)
MiST1 Rucaparib
BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.
干预措施: Rucaparib (Drug)
结局指标
主要结局
Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
时间窗: 12 weeks
This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria reporting. Scans will be undertaken every 6 weeks. Analysis will be timed from study entry using the baseline CT scan results until completion of treatment cycles, confirmed disease progression or death - whichever comes first.
Disease Control Rate (DCR) at 12 Weeks Assessed by Modified RECIST 1.1, in Patients With Relapsed Mesothelioma.
时间窗: 12 weeks
This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria reporting. Scans will be undertaken every 6 weeks. Analysis will be timed from study entry using the baseline CT scan results until completion of treatment cycles, confirmed disease progression or death-whichever comes first. Complete response (CR): disappearance of all target and non-target lesions with no evidence of tumour elsewhere Partial response (PR): reduction of at least 30% in the sum of all measurements with no evidence of significant disease progression in non-target lesions or new lesions Progressive disease (PD): 1: increase of at least 20% in the sum of all measurements compared with the previous best response, 2: appearance of one or more significant (overall 20% increase in tumour diameters) new lesions, 3: significant increase in target lesions Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD
次要结局
- Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.(24 weeks)
- Objective response rate (ORR) assessed for 12 months(Up to 12 months (up to 6 months during treatment and 6 months of follow-up))
- Safety assessed according to CTCAE criteria.(12 months (up to 6 months during treatment and 6 months of follow-up))
- Toxicity assessed according to CTCAE criteria.(12 months (up to 6 months during treatment and 6 months of follow-up))
- Disease Control Rate (DCR) at 24 Weeks Assessed by Modified RECIST 1.1, in Patients With Relapsed Mesothelioma.(24 weeks)
- Objective Response Rate (ORR) at 24 Weeks Assessed by Modified RECIST 1.1, in Patients With Relapsed Mesothelioma.(24 weeks)