Ignite Creation Date:
2025-12-25 @ 5:05 AM
Ignite Modification Date:
2025-12-26 @ 4:08 AM
Study NCT ID:
NCT04601727
Status:
COMPLETED
Last Update Posted:
2023-05-11
First Post:
2020-09-21
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Oral & Faecal Microbiota Analysis in Patients With Rectal Cancer Requiring Pre-operative Therapy Before Surgery, & Correlation With Response
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012004', 'term': 'Rectal Neoplasms'}], 'ancestors': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D003672', 'term': 'Defecation'}], 'ancestors': [{'id': 'D004068', 'term': 'Digestive System Physiological Phenomena'}, {'id': 'D055688', 'term': 'Digestive System and Oral Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': '16srRNA analysis of faeces and saliva before and after neoadjuvant chemoradiotherapy'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-05', 'completionDateStruct': {'date': '2022-05-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-05-10', 'studyFirstSubmitDate': '2020-09-21', 'studyFirstSubmitQcDate': '2020-10-19', 'lastUpdatePostDateStruct': {'date': '2023-05-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-10-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-03-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '16s rRNA pyrosequencing analysis of microbial flora of rectal cancer patients', 'timeFrame': '1 year', 'description': 'The microbial flora of the saliva and faeces of patients will be analysed at two time points. 1. before neoadjuvant chemoradiotherapy and 2. prior to surgery. This will be 16SrRNA pyrosequencing analysis to plot the microbial flora of each sample'}], 'secondaryOutcomes': [{'measure': 'Categorisation of microbial flora against response to neoadjuvant chemoradiotherapy', 'timeFrame': '1 year', 'description': 'The pathology resection specimen will be divided into four categories in terms of response to neoadjuvant chemoradiotherapy. 1. complete response, 2. good partial, 3, minimal and 4. complete response. These groupings will be used to analyse if there are any differences in microbial flora which may be able to predict for response to therapy'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Rectal Cancer']}, 'descriptionModule': {'briefSummary': 'Rectal cancer is a common pathology which is treated by a multimodal approach. Those tumours in the rectum that are locally advanced are treated with neoadjuvant chemoradiotherapy before an operation. This aims to reduce the size of the tumour and increase the change of a complete resection. The degree of shrinkage of a rectal cancer to pre-operative treatment is influenced by the immune system. In some other cancers there is evidence that the bacteria living in our mouth \\& in the large bowel influence the way the body responds a cancer. In this study patients with rectal cancer requiring radiotherapy before surgery will be asked to give samples of saliva \\& bowel motions before chemoradiotherapy \\& again before surgery. These samples will have the type and number of bacteria analysed, as well as levels of key metabolic products of these bacteria. The results will be compared with the response, as assessed by the pathologist using standard criteria, of the rectal to the radiotherapy.', 'detailedDescription': "Introduction:\n\nPelvic radiotherapy (VMAT) and chemotherapy are used in margin threatened rectal cancer to reduce the cancer and achieve a clear circumferential resection margin (CRM), facilitating potentially curative surgery. In 15 to 20% of cases, the pre-operative chemoradiotherapy potentially completely treats the cancer raising the possibility to avoid surgery altogether. Increasing the number of patients who are able to be cured without surgery is a research priority for the NCRI Colorectal Studies Group in UK. Other patients have some reduction in the size of the malignancy (a partial response) and others have a minimal response to the pre-operative therapy. As yet, it remains unclear as to the mechanism of response of the cancer to neoadjuvant therapy.\n\nUnderstanding what biological factors influence response is important in order to improve the outcomes in rectal cancer. There is evidence that the innate immune system has a role in the degree of response. An increased degree of response (as measured by tumour regression grading) is associated with an increased abundance of natural killer (NK) CD56+ve cells. In mouse models the gut microbiome can modulate the tumour-immune microenvironment and T cell responses in colonic cancer. In addition some bacteria that are associated with colorectal cancer, such as F. nucleatum, are indigenous to the human oral cavity, and evidence that patients with colorectal cancer have a distinctive oral microbiota.\n\nClinical studies are needed to investigate the role of the oral \\& faecal microbiome in response to pre-operative treatment. If there is evidence of an association, the challenge will then be to explore if this can be modulated to increase response. Alternatively, the pre treatment microbiota profile may be able to be used as a predictor of response to neoadjuvant therapy.\n\nThis is a pilot study to assess the feasibility and acceptability to patients in providing faecal and saliva samples before cancer treatment. The investigators will also assess if there are any potential links between host microbial flora and chemoradiotherapy response\n\nStudy design:\n\nPatients with a biopsy proven rectal adenocarcinoma have staging investigations, and these are discussed at a Colorectal Cancer (CRC) Multi- Disciplinary Team (MDT). If the CRM is threatened or involved then it would be standard practice to recommend pre-operative radiotherapy.\n\nThe 1st step for eligible patients is allocation to a consultant colorectal surgeon, who will meet the patient to confirm the standard plan for treatment.\n\nThe 2nd step is arranging an out-patient appointment to see a clinical oncologist. At this appointment the rationale, practical aspects and potential side effects of pre-operative therapy are discussed. In addition, the 3rd step, which is a discussion around the study plan, to collect and analyse both oral \\& faecal microbiota pre-pelvic treatment \\& again pre-surgery will be undertaken. A written patient information sheet is given to the patient to consider at home.\n\nPelvic radiotherapy is given as an out-patient. The first step is contouring the relevant anatomy, including tumour \\& associated lymph nodes, as well as normal organs that we want to limit the dose of radiation received. This contouring \\& preparation of a radiotherapy plan can take up to two weeks, so there is plenty of time for the 4th step, namely the patient considering whether they wish to take part in the study. If the patient decides to enter the study, they will sign \\& date a consent form.\n\nStep 5 - For patients who decide to enter the study, the 5th step is arranging for collection of both oral \\& faecal samples for analysis before starting the pelvic radiotherapy (as an out-patient). The oral sample will be collected in the radiotherapy department prior to the first treatment, and the patient can choose to collect the faecal sample either at home or in the clinic, both on the day they are due to start the radiotherapy.\n\nThe patient continues on the radiotherapy and on completion there is a deliberately a 7 to 8 week wait, to allow the treatment to have an effect on the tumour, as well as allowing for any side effects to settle. After the treatment gap, the patient has another pelvic MRI scan, reviewed at a CRC MDT, to assess if the CRM is now clear, allowing the patient to proceed to potentially curative surgery.\n\nStep 6 - For patients with a clear CRM a second set of oral \\& faecal samples for analysis will be collected the day prior to surgery. Again the patient has the option of collecting the faecal donation at home, and bringing it with them, or in clinic.\n\nStep 7 - The surgical specimen is collected from theatre \\& brought directly to the pathology department by a member of the biodepository staff, as per standard practice. The pathologist, together with a member of the biodepository staff will collect samples from the lumen of the specimen, from the tumour \\& distant normal mucosa for microbiota \\& metabolite analysis. The tumour itself is assessed using a standardised approach, and any response graded using a validated \\& published system.\n\nStep 8 - Comparison of the results pre- post- pelvic radiotherapy microbiota \\& metabolites, and an initial comparison with the pathology response grading. As there is a 15-20% possibility of a complete clinical response (cCR), these patients may wish to enter the 'active surveillance' programme. The faecal and oral microbiota of the cCR will also be analysed during this study. The samples of those individuals who do not have a clear CRM and do not progress to surgery will be analysed as a separate subgroup of the cohort\n\nThere will be no requirement for additional clinic visits for any patients taking part in the study. There will be additional time during the initial clinic visits, to discuss the study \\& answer any questions. Obtaining written consent will be timed with one of the visits for radiotherapy planning \\& preparation, and, as there is a 60 minute wait for oral contrast to reach the small bowel during the first radiotherapy CT simulator visit, there will not be any additional time waiting for the patient.\n\nThe collection of all study samples will be coordinated with routine visits to hospital, to ensure no additional visits would be required for a patient taking part in the study. A total of 25 patients will be recruited."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Locally advanced rectal cancer patients suitable for neoadjuvant chemoradiotherapy', 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adult patients with a locally advanced rectal cancer (defined as CRM threatening on MRI scans) in whom neoadjuvant chemoradiotherapy has been offered before consideration of curative resection\n* must be able to consent to inclusion in project\n\nExclusion Criteria:\n\n* Anyone who does not consent for inclusion\n* Any non rectal adenocarcinoma\n* Early rectal cancers that do not require neoadjuvant therapy\n* Patients presenting as an emergency with an obstructing rectal cancer requiring an early resection\n* Patients who are treated with short course radiotherapy alone rather than long course chemoradiotherapy'}, 'identificationModule': {'nctId': 'NCT04601727', 'acronym': 'MICROBRECT', 'briefTitle': 'Oral & Faecal Microbiota Analysis in Patients With Rectal Cancer Requiring Pre-operative Therapy Before Surgery, & Correlation With Response', 'organization': {'class': 'OTHER', 'fullName': 'University of Aberdeen'}, 'officialTitle': 'Oral & Faecal Microbiota Analysis in Patients With Rectal Cancer Requiring Pre-operative Therapy Before Surgery, & Correlation With Response. (The MicrobRect Study).', 'orgStudyIdInfo': {'id': '2-014-20'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Rectal cancer patients', 'interventionNames': ['Diagnostic Test: 16srRNA pyrosequencing analysis of microbiota of saliva and faeces']}], 'interventions': [{'name': '16srRNA pyrosequencing analysis of microbiota of saliva and faeces', 'type': 'DIAGNOSTIC_TEST', 'description': 'No intervention in this study', 'armGroupLabels': ['Rectal cancer patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'AB25 2ZN', 'city': 'Aberdeen', 'state': 'Scotland', 'country': 'United Kingdom', 'facility': 'Aberdeen Royal Infirmary', 'geoPoint': {'lat': 57.14369, 'lon': -2.09814}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Aberdeen', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}