Microbiome Immunotherapy Toxicity and Response Evaluation
An Observational Study to Evaluate the Microbiome as a Biomarker of Efficacy and Toxicity in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
2 other identifiers
observational
1,800
1 country
13
Brief Summary
This is a observational study to investigate how the microbiome correlates with efficacy and toxicity of immune checkpoint inhibitors in patients with advanced cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jul 2020
Longer than P75 for all trials
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 9, 2019
CompletedFirst Posted
Study publicly available on registry
September 27, 2019
CompletedStudy Start
First participant enrolled
July 8, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 8, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 8, 2025
CompletedFebruary 16, 2023
February 1, 2023
4 years
September 9, 2019
February 15, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Can the microbiome signature predict progression-free survival (PFS) of 1 year or greater
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).
Minimum 1 year PFS
Secondary Outcomes (8)
Can the microbiome signature predict PFS
1 year & 2 years PFS
Can the microbiome signature overall survival (OS)
Up to 6 years
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
Correlate microbiome findings with incidence and characteristics of immune-related adverse events
Up to 6 years
- +3 more secondary outcomes
Study Arms (9)
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.
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.
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.
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.
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.
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.
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.
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.
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.
Interventions
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).
A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).
A fully human monoclonal antibody raised to target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).
A humanised IgG1 monoclonal antibody raised to target vascular endothelial growth factor (VEGF).
Eligibility Criteria
Up to 1800 cancer patients due to receive anti-PD(L)1 +/- anti-CTLA-4 antibodies for treatment of their cancer and up to 360 consenting adults (household controls) who live with one of these cancer patients.
You may qualify if:
- Signed informed consent
- Aged ≥18 years old
- Histological or cytological confirmation of invasive malignancy
- Due to commence palliative, adjuvant or neoadjuvant systemic therapy including an anti-PD-(L)1 antibody +/- anti-CTLA-4 antibody
- Patients with unresectable disease must have radiologically and/or clinically measurable disease, by RECIST version 1.1; target lesions must not have been previously irradiated; baseline tumour assessments must be performed within 45 days prior to starting immune checkpoint inhibitor treatment
- Received no prior immune checkpoint inhibitors (previous treatment with other types of anti-cancer therapy is determined by patient cohort; for patients with unresectable disease, prior adjuvant therapy with immune checkpoint inhibitor(s) is allowed).
- Willing and able to comply with scheduled visits, treatment plans, sample collections and other study procedures
You may not qualify if:
- Other invasive malignancies diagnosed within the last year which are not fully resected, or in complete remission, or for which additional therapy is required
- Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk, or interfere with their ability to comply with the study. Examples may include, but are not limited to:
- Patients with uncontrolled ischaemic heart or other cardiovascular event (e.g. myocardial infarction, new angina, stroke, transient ischaemic attack, or new congestive cardiac failure) within the last 6 months
- Presence of active infection
- Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C
- Current active, severe, or uncontrolled autoimmune condition, including but not limited to Crohn's disease and ulcerative colitis.
- Women who are pregnant, plan to become pregnant or are lactating during the study period.
- Requirement for non-physiological dose of oral steroids, or regular use of any other immunosuppressive agents; less than 10mg prednisolone or equivalent doses are allowed. Use of inhaled or topical steroids is allowed.
- Household control eligibility requirements:
- Confirmation of suitability to be a household control participant will be determined by completing a self-assessed questionnaire either at home or in clinic.
- Household controls must:
- NOT have had any gastrointestinal infections i.e., parasites, viruses or diarrhoeal episodes during the last 6 months.
- NOT have taken antibiotics for at least 6 months
- NOT have or be recovering from any chronic intestinal disease such as:
- Crohn's disease
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CCTU- Cancer Themelead
- Microbiotica Ltdcollaborator
Study Sites (13)
Royal United Hospitals Bath NHS Foundation Trust
Bath, BA1 3NG, United Kingdom
University Hospitals Dorest NHS Foundation Trust
Bournemouth, BH7 7DW, United Kingdom
University Hospitals Bristol NHS Foundation Trust
Bristol, BS2 8ED, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ, United Kingdom
Velindre University NHS Trust
Cardiff, CF14 2TL, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust
Kings Lynn, United Kingdom
University Hospitals of Leicester NHS Foundation Trust
Leicester, LE1 5WW, United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, NR4 7UY, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S10 2SJ, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD, United Kingdom
Somerset NHS Foundation Trust
Taunton, TA1 5DA, United Kingdom
Royal Cornwall Hospitals NHS Trust
Truro, TR1 3LJ, United Kingdom
Related Publications (1)
Thompson NA, Stewart GD, Welsh SJ, Doherty GJ, Robinson MJ, Neville BA, Vervier K, Harris SR, Adams DJ, Dalchau K, Bruce D, Demiris N, Lawley TD, Corrie PG. The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy. BMC Cancer. 2022 Jan 24;22(1):99. doi: 10.1186/s12885-021-09156-x.
PMID: 35073853DERIVED
Biospecimen
Research blood samples, saliva samples and stool samples collected. Tumour samples and organ sample after toxicity if available. A single, optional nasopharyngeal swab for COVID-19 may be offered to participants before study entry.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pippa Corrie
Cambridge University Hospital
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Dr Pippa Corrie, Chief Investigator
Study Record Dates
First Submitted
September 9, 2019
First Posted
September 27, 2019
Study Start
July 8, 2020
Primary Completion
July 8, 2024
Study Completion
July 8, 2025
Last Updated
February 16, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will not share