MITRE
Research type
Research Study
Full title
MITRE: Microbiome Immunotherapy Toxicity and Response Evaluation. A study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy
IRAS ID
271456
Contact name
Stephen Kelleher
Contact email
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
There is increasing evidence that the bacteria that live naturally in our mouth and gut (called our ‘microbiome’) influence our immune system and how it works. The mix of bacteria living in your microbiome is unique to you and this is affected by various factors, including your diet, your medications and where you live. Recently, some small studies have linked the presence of certain bacteria in a patient’s microbiome with the effectiveness of immunotherapy for cancer, particularly immune checkpoint inhibitor drugs that they have taken.\n\nImmune checkpoint inhibitor drugs are improving outcomes for cancer patients, these drugs work by reactivating immune cells to recognise and kill cancerous cells. However, these drugs do not work for everyone and they can also cause some people side effects that are difficult to tolerate. We would like to be able to identify patients who are likely to either benefit or experience side effects from these drugs, which we cannot do currently. Previous research has mainly focussed on looking for markers in blood and tumour samples that these drugs are working or causing toxicity. We plan to undertake a detailed study of the mouth and gut bacteria of patients receiving treatment with these drugs by collecting an oral swab sample prior to treatment as well as a series of stool samples prior to and during treatment. We will collect blood samples and also tumour tissue, if it is available to us. After we analyse these samples, we hope to better understand how the microbiome contributes to the effectiveness of immune checkpoint inhibitor drugs as well as potential side effects. We hope we can use this knowledge to tailor patient treatment and potentially develop better treatments in the future.\n\nWe plan to recruit up to 1800 patients and 360 household controls over a 5 year period. \n[COVID-19 amendment 08/07/2020]; Due to the current COVID-19 pandemic, we have amended the protocol in order to ascertain any correlations between COVID-19 and the microbiome. National arrangements for routine population and cancer patient COVID-19\ntesting are evolving and are likely to continue to change during the course of the study. We wish to evaluate both COVID-19 antigen and antibody associations with the microbiome and this will involve testing blood, stool and nasopharyngeal swab. We will aim to use results available from routine testing where possible, which currently focusses on nasopharyngeal swab tests for COVID-19 antigen, although could include blood testing for antibodies in the\nforeseeable future. In the absence of routine testing for either or both of these entities, we wish to include the option to test within the amended protocol.\nWe are making 3 specific requests to our patients and household control participants, all of which are optional.\n1) We wish to collect information from patients and household controls regarding previous testing and treatment for COVID-19.\n2) If participants have not had a routine assessment of COVID-19 antigen from a nasopaharyngeal swab within 4 weeks of study entry, we would like to offer them the option of this being collected and tested locally. We had not previously planned to collect a nasopharyngeal swab, so this has been added to the protocol.\n3) Our protocol already allows us to collect and therefore test blood and stool for COVID-19 and this has now been made explicit in the protocol and COVID-19 related PIS/consent form.\nAny standard tests e.g. nasopharyngeal swab test antigen results will be reported back to the participant and managed according to local practice. Testing of blood and stool are not standard and as research tests will not be immediately made available to the participant. However, if they do become standardised over time, the results will be\nmade available and this is made clear in the consent process.\nTo explain this new COVID-19-related part of our research to study participants and to obtain their consent, we have created separate information sheet/consent forms for cancer patients and household controls. Consent to this section of the study is optional.\nThe protocol processes have been revised to facilitate remote clinic assessments and allow remote consent. These changes are intended to limit risks to patients and household controls which include reducing/avoiding the need for face-to-face hospital visits during the COVID-19 pandemic. The Organisation Information Document (OID) and Schedule of Events Cost Attribution Tool (SoECAT) for this study\nhave also been updated to include the option of a single, optional nasopharyngeal swab to test for COVID-19 antigen prior to study entry for each participant.\nOur original patient and household control information sheets and informed consent forms have been updated to include link to an online clinical trials database curated by Cancer Research UK (CRUK). This has been added as it is requirement of the funding awarded by CRUK. Also, the self-assessed health information questionnaire included\nin the household control PIS has been updated. This now includes the eligibility requirement of the potential participant having not been hospitalised for treatment of COVID-19 within the last 6 months, to reflect changes made to the protocol (section 15.3 and appendix 4).\nFinally, in order to aid the collection of information on the social, family history and lifestyle habits of participants, participant-facing questionnaire has been produced to collect this information. This will only be given to participants who have consented to take part in the study and they will only need to complete it at study entry. Their responses will be reviewed by a member of the local research team. This is a non-validated question, however it has been produced to align to the demographic details in our REC-approved protocol and aid data collection. It was suggested to us following discussion with our local research nurses experienced in recruiting patients and collecting research data, who felt this would greatly enhance the quality of information being obtained.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
19/EE/0358
Date of REC Opinion
31 Jan 2020
REC opinion
Further Information Favourable Opinion