- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04107168
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: MITRE Study Coordinator
- Phone Number: 01223 274746
- Email: cuh.mitre@nhs.net
Study Locations
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-
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Bath, United Kingdom, BA1 3NG
- Recruiting
- Royal United Hospitals Bath NHS Foundation Trust
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Bournemouth, United Kingdom, BH7 7DW
- Recruiting
- University Hospitals Dorest NHS Foundation Trust
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Bristol, United Kingdom, BS2 8ED
- Recruiting
- University Hospitals Bristol NHS Foundation Trust
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Cambridge, United Kingdom, CB2 0QQ
- Recruiting
- Cambridge University Hospitals NHS Foundation Trust
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Cardiff, United Kingdom, CF14 2TL
- Recruiting
- Velindre University NHS Trust
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Edinburgh, United Kingdom, EH4 2XU
- Recruiting
- Western General Hospital
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King's Lynn, United Kingdom
- Recruiting
- The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust
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Leicester, United Kingdom, LE1 5WW
- Recruiting
- University Hospitals of Leicester NHS Foundation Trust
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Norwich, United Kingdom, NR4 7UY
- Recruiting
- Norfolk and Norwich University Hospitals NHS Foundation Trust
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Sheffield, United Kingdom, S10 2SJ
- Recruiting
- Sheffield Teaching Hospitals NHS Foundation Trust
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Southampton, United Kingdom, SO16 6YD
- Recruiting
- University Hospital Southampton NHS Foundation Trust
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Taunton, United Kingdom, TA1 5DA
- Recruiting
- Somerset NHS Foundation Trust
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Truro, United Kingdom, TR1 3LJ
- Recruiting
- Royal Cornwall Hospitals NHS Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria for cancer patients:
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
Exclusion Criteria for cancer patients:
- 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
- Ulcerative colitis
- Coeliac disease
- Irritable bowel syndrome
- Stomach ulcers
- NOT have a chronic autoimmune disease or significant allergies e.g., multiple sclerosis, asthma requiring regular medication, psoriasis.
- NOT have and NOT be recovering from any form of cancer.
- NOT take proton pump inhibitors, steroids, other non-steroidal anti-inflammatory drugs such as ibuprofen or aspirin.
- NOT had requirement to be hospitalised for treatment of COVID-19
In addition, household controls must sign informed consent and be aged ≥18 years old.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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. |
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
Other Names:
A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
Other Names:
A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).
Other Names:
A humanised IgG1 monoclonal antibody raised to target vascular endothelial growth factor (VEGF).
Other Names:
|
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.
|
A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
Other Names:
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
Other Names:
|
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.
|
A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).
Other Names:
A fully human monoclonal antibody raised to target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
Other Names:
|
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.
|
A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
Other Names:
A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Can the microbiome signature predict progression-free survival (PFS) of 1 year or greater
Time Frame: 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).
|
Minimum 1 year PFS
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Can the microbiome signature predict PFS
Time Frame: 1 year & 2 years PFS
|
Measure the ability of the microbiome signature to predict 6 month PFS, 2 year PFS, overall response rate and median PFS in Cohorts 1-6.
|
1 year & 2 years PFS
|
Can the microbiome signature overall survival (OS)
Time Frame: Up to 6 years
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Measure the ability of the microbiome signature to median OS in Cohorts 1-6.
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Up to 6 years
|
Can the microbiome signature to predict relapse
Time Frame: 1 year & 2 years relapse-free survival (RFS)
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Measure the ability of the microbiome signature to predict for 1 or 2 year relapse after resection of high risk melanoma or renal cancer in cohorts 7-9.
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1 year & 2 years relapse-free survival (RFS)
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Does the microbiome correlate with treatment efficacy
Time Frame: Up to 6 years
|
To compare pre-treatment oral and gut microbiome findings and their association with treatment efficacy.
|
Up to 6 years
|
Correlate microbiome findings with incidence and characteristics of immune-related adverse events
Time Frame: Up to 6 years
|
To correlate microbiome findings with incidence and characteristics of CTCAE V5-defined Grade 3 or greater immune-related adverse events in all enrolled cancer patients, and any association with response to immunosuppressants.
|
Up to 6 years
|
Correlation microbiome findings and known characteristics of patients
Time Frame: Up to 6 years
|
To correlate microbiome findings with aspects of pre-existing patient characteristics and behaviour including but not limited to diet, smoking history, BMI, use of antibiotics, steroids, proton pump inhibitors, non-steroidal anti-inflammatory drugs and probiotics.
|
Up to 6 years
|
Control for the microbiome of cancer patients
Time Frame: Up to 6 years
|
To compare the microbiome signature of cancer patients with a household control group of people who are not known to have cancer.
|
Up to 6 years
|
Build a library of biological samples for future research
Time Frame: Up to 6 years
|
To retain a library of biological samples (saliva, stool, blood and tumour as well as organ if available) with linked patient data for future research.
|
Up to 6 years
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Kidney Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Nivolumab
- Durvalumab
- Tremelimumab
- Bevacizumab
- Pembrolizumab
- Ipilimumab
- Atezolizumab
Other Study ID Numbers
- MITRE
- C7535/A27717 (Other Grant/Funding Number: Cancer Research UK)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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