Microbiome Immunotherapy Toxicity and Response Evaluation

NCT ID: NCT04107168

Last Updated: 2023-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

1800 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-07-08

Study Completion Date

2025-07-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a observational study to investigate how the microbiome correlates with efficacy and toxicity of immune checkpoint inhibitors in patients with advanced cancer.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Melanoma Renal Cancer Lung Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Pembrolizumab

Intervention Type DRUG

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Ipilimumab

Intervention Type DRUG

A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Ipilimumab

Intervention Type DRUG

A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Pembrolizumab

Intervention Type DRUG

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

Atezolizumab

Intervention Type DRUG

A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Pembrolizumab

Intervention Type DRUG

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

Atezolizumab

Intervention Type DRUG

A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).

Bevacizumab

Intervention Type DRUG

A humanised IgG1 monoclonal antibody raised to target vascular endothelial growth factor (VEGF).

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.

Nivolumab

Intervention Type DRUG

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Pembrolizumab

Intervention Type DRUG

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

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.

Pembrolizumab

Intervention Type DRUG

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

Durvalumab

Intervention Type DRUG

A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).

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.

Durvalumab

Intervention Type DRUG

A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).

Tremelimumab

Intervention Type DRUG

A fully human monoclonal antibody raised to target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Nivolumab

A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).

Intervention Type DRUG

Pembrolizumab

A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.

Intervention Type DRUG

Ipilimumab

A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).

Intervention Type DRUG

Durvalumab

A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).

Intervention Type DRUG

Tremelimumab

A fully human monoclonal antibody raised to target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).

Intervention Type DRUG

Atezolizumab

A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).

Intervention Type DRUG

Bevacizumab

A humanised IgG1 monoclonal antibody raised to target vascular endothelial growth factor (VEGF).

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Opdivo Keytruda Yervoy Imfinzi CP-675,206 Tecentriq Avastin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Microbiotica Ltd

INDUSTRY

Sponsor Role collaborator

CCTU- Cancer Theme

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

CCTU- Cancer Theme

Dr Pippa Corrie, Chief Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pippa Corrie

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Royal United Hospitals Bath NHS Foundation Trust

Bath, , United Kingdom

Site Status RECRUITING

University Hospitals Dorest NHS Foundation Trust

Bournemouth, , United Kingdom

Site Status RECRUITING

University Hospitals Bristol NHS Foundation Trust

Bristol, , United Kingdom

Site Status RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status RECRUITING

Velindre University NHS Trust

Cardiff, , United Kingdom

Site Status RECRUITING

Western General Hospital

Edinburgh, , United Kingdom

Site Status RECRUITING

The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

Kings Lynn, , United Kingdom

Site Status RECRUITING

University Hospitals of Leicester NHS Foundation Trust

Leicester, , United Kingdom

Site Status RECRUITING

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Site Status RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status RECRUITING

Somerset NHS Foundation Trust

Taunton, , United Kingdom

Site Status RECRUITING

Royal Cornwall Hospitals NHS Trust

Truro, , United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

MITRE Study Coordinator

Role: CONTACT

01223 274746

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 35073853 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

C7535/A27717

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MITRE

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Study of LY2801653 in Advanced Cancer
NCT01285037 COMPLETED PHASE1
The Rechallenge of ADCs in MBC Patients
NCT05571618 ACTIVE_NOT_RECRUITING