An Observational Study to Evaluate the Microbiome as a Biomarker of Efficacy and Toxicity in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,800
- 试验地点
- 13
- 主要终点
- Can the microbiome signature predict progression-free survival (PFS) of 1 year or greater
研究概览
简要总结
This is a observational study to investigate how the microbiome correlates with efficacy and toxicity of immune checkpoint inhibitors in patients with advanced cancer.
详细描述
The gastrointestinal microbiome of a healthy individual is comprised of many hundreds of bacteria species and thousands of bacteria strains. The composition of bacteria in an individual's microbiome can change over time and this can be influenced by factors including diet, drugs, genetics and infection. These bacteria play a central role in digestion of food, development and regulation of our immune system as well as our resistance to pathogens. Recent evidence suggest that a patient's intestinal microbiota composition plays a critical, though as yet poorly defined, role in determining both therapeutic efficacy and likelihood of significant adverse events to T-cell checkpoint inhibitor immunotherapy.
Immune checkpoint inhibitors are revolutionising treatment of many types of metastatic cancer, including melanoma, renal and non-small cell lung cancer, in the expectation of improving patient overall survival. However, they have limitations as they do not work for all patients and can cause unpredictable, complex immune-related toxicities. The investigators will perform a detailed study of cancer patients receiving checkpoint inhibitors. Saliva and a series of stool samples will be collected from each patient to analyse their microbiome and will be linked to treatment response, by examining blood samples and - if available - tumour and organ samples. The investigators hope this work will enable personalisation of patient immunotherapies based on microbiome biomarkers, as well as precisely manipulate a patient's microbiota to optimise their immunotherapy.
In addition, participants who have consented to take part in an optional sub-study may be offered a single nasopharyngeal swab for COVID-19 antigen before study entry. The investigators hope that that this identify correlations between the microbiome and COVID-19.
Comparison with a limited cohort of healthy household members (up to 360 volunteers) acting as controls will provide additional essential information about the role of the patient-specific microbiome.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1
Disease: Unresectable AJCC (American Joint Committee on Cancer) stage 3 or 4 melanoma.
Anti-PD-1 monotherapy (Nivolumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 1
Disease: Unresectable AJCC (American Joint Committee on Cancer) stage 3 or 4 melanoma.
Anti-PD-1 monotherapy (Nivolumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Pembrolizumab (Drug)
Cohort 2
Disease: Unresectable AJCC stage 3 or 4 melanoma. Nivolumab + Ipilimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 2
Disease: Unresectable AJCC stage 3 or 4 melanoma. Nivolumab + Ipilimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Ipilimumab (Drug)
Cohort 3
Disease: Advanced renal cell carcinoma. Anti-PD-(L)1 + kinase inhibitor. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 4
Disease: Advanced renal cell carcinoma Nivolumab + Ipilimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 4
Disease: Advanced renal cell carcinoma Nivolumab + Ipilimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Ipilimumab (Drug)
Cohort 5
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) monotherapy in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 5
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) monotherapy in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Pembrolizumab (Drug)
Cohort 5
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) monotherapy in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Atezolizumab (Drug)
Cohort 6
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) + chemotherapy +/- antiangiogenic (Bevacizumab) in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 6
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) + chemotherapy +/- antiangiogenic (Bevacizumab) in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Pembrolizumab (Drug)
Cohort 6
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) + chemotherapy +/- antiangiogenic (Bevacizumab) in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Atezolizumab (Drug)
Cohort 6
Disease: Advanced NSCLC Anti-PD-(L)1 (Nivolumab, Pembrolizumab or Atezolizumab) + chemotherapy +/- antiangiogenic (Bevacizumab) in the first line setting. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Bevacizumab (Drug)
Cohort 7
Disease: Resected AJCC stage 3 or 4 melanoma. Anti-PD-1 monotherapy (Nivolumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Nivolumab (Drug)
Cohort 7
Disease: Resected AJCC stage 3 or 4 melanoma. Anti-PD-1 monotherapy (Nivolumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Pembrolizumab (Drug)
Cohort 8
Disease: Resected renal cancer Anti-PD-(L)1 monotherapy (Durvalumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Pembrolizumab (Drug)
Cohort 8
Disease: Resected renal cancer Anti-PD-(L)1 monotherapy (Durvalumab or Pembrolizumab). Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Durvalumab (Drug)
Cohort 9
Disease: Resected renal cancer Durvalumab + Tremelimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Durvalumab (Drug)
Cohort 9
Disease: Resected renal cancer Durvalumab + Tremelimumab. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted.
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Can the microbiome signature predict progression-free survival (PFS) of 1 year or greater
时间窗: Minimum 1 year PFS
The primary outcome measure is the ability to predict for PFS of 1 year or greater for patients with advanced melanoma, renal and non-small cell lung cancer (cohorts 1-6).
次要结局
- Can the microbiome signature to predict relapse(1 year & 2 years relapse-free survival (RFS))
- Does the microbiome correlate with treatment efficacy(Up to 6 years)
- Build a library of biological samples for future research(Up to 6 years)
- Can the microbiome signature predict PFS(1 year & 2 years PFS)
- Can the microbiome signature overall survival (OS)(Up to 6 years)
- Correlate microbiome findings with incidence and characteristics of immune-related adverse events(Up to 6 years)
- Correlation microbiome findings and known characteristics of patients(Up to 6 years)
- Control for the microbiome of cancer patients(Up to 6 years)
研究者
CCTU- Cancer Theme
Dr Pippa Corrie, Chief Investigator
Cambridge University Hospitals NHS Foundation Trust