Ignite Creation Date:
2025-12-24 @ 2:07 PM
Ignite Modification Date:
2026-02-02 @ 4:40 AM
Study NCT ID:
NCT03039595
Status:
COMPLETED
Last Update Posted:
2022-06-09
First Post:
2017-01-30
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Ploidy and Stroma in Early Rectal Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': True, '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': 'D011003', 'term': 'Ploidies'}], 'ancestors': [{'id': 'D055614', 'term': 'Genetic Phenomena'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'helen.jones3@ouh.nhs.uk', 'phone': '01865 235657', 'title': 'Dr Helen Jones', 'organization': 'Oxford Univeristy Hospitals NHS Foundation Trust'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'Up to 12 years following surgery', 'eventGroups': [{'id': 'EG000', 'title': 'Patients', 'description': 'All patients', 'otherNumAtRisk': 143, 'deathsNumAtRisk': 143, 'otherNumAffected': 0, 'seriousNumAtRisk': 143, 'deathsNumAffected': 27, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Correlation Between Ploidy Status With Local Recurrence of Cancer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '140', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Patients', 'description': 'All patients'}], 'classes': [{'categories': [{'title': 'Diploid - Local recurrence', 'measurements': [{'value': '3', 'groupId': 'OG000'}]}, {'title': 'Diploid - No local recurrence', 'measurements': [{'value': '31', 'groupId': 'OG000'}]}, {'title': 'Non-diploid - Local recurrence', 'measurements': [{'value': '14', 'groupId': 'OG000'}]}, {'title': 'Non-diploid - No local recurrence', 'measurements': [{'value': '92', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Only patients for whom ploidy status was available were included in the analysis (ploidy assessment failed in 3 patients for technical reasons)'}, {'type': 'PRIMARY', 'title': 'Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Patients', 'description': 'All patients'}], 'classes': [{'categories': [{'title': 'High TSR - Local recurrence', 'measurements': [{'value': '2', 'groupId': 'OG000'}]}, {'title': 'High TSR - No local recurrence', 'measurements': [{'value': '9', 'groupId': 'OG000'}]}, {'title': 'Low TSR - Local recurrence', 'measurements': [{'value': '17', 'groupId': 'OG000'}]}, {'title': 'Low TSR - No local recurrence', 'measurements': [{'value': '115', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '140', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Patients', 'description': 'All patients'}], 'classes': [{'categories': [{'title': 'Diploid - Alive', 'measurements': [{'value': '27', 'groupId': 'OG000'}]}, {'title': 'Diploid - Deceased', 'measurements': [{'value': '7', 'groupId': 'OG000'}]}, {'title': 'Non-diploid - Alive', 'measurements': [{'value': '86', 'groupId': 'OG000'}]}, {'title': 'Non-diploid - Deceased', 'measurements': [{'value': '20', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Patients', 'description': 'All patients'}], 'classes': [{'categories': [{'title': 'High TSR - Alive', 'measurements': [{'value': '6', 'groupId': 'OG000'}]}, {'title': 'High TSR - Deceased', 'measurements': [{'value': '5', 'groupId': 'OG000'}]}, {'title': 'Low TSR - Alive', 'measurements': [{'value': '110', 'groupId': 'OG000'}]}, {'title': 'Low TSR - Deceased', 'measurements': [{'value': '22', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Patients', 'description': 'All patients. This is an observational study; no interventions were used.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '150'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '143'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Patients', 'description': 'All patients'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '69', 'groupId': 'BG000', 'lowerLimit': '38', 'upperLimit': '94'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '56', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '87', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United Kingdom', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '143', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Tumour stage', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'categories': [{'title': 'pT1 (tumour confined to the inner layer of the bowel)', 'measurements': [{'value': '76', 'groupId': 'BG000'}]}, {'title': 'pT2 (tumour extends into the muscle layer of the bowel wall)', 'measurements': [{'value': '58', 'groupId': 'BG000'}]}, {'title': 'pT3 (tumour has reached the outer lining of the bowel wall)', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Tumour component of the TNM (Tumour, Node, Metastasis) staging system determined by histopathological analysis of the resected tumour.', 'unitOfMeasure': 'Participants'}, {'title': 'Post-TEM management', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Surveillance', 'measurements': [{'value': '88', 'groupId': 'BG000'}]}, {'title': 'Completion radical surgery', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}, {'title': 'Adjuvant radiotherapy', 'measurements': [{'value': '42', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-10-21', 'size': 264620, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-01-07T06:58', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Specimens of early rectal cancer removed by transanal endoscopic microsurgery, which are routinely retained, will be further analysed.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 150}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-03-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-03', 'completionDateStruct': {'date': '2019-07-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-03-09', 'studyFirstSubmitDate': '2017-01-30', 'resultsFirstSubmitDate': '2022-01-10', 'studyFirstSubmitQcDate': '2017-01-30', 'lastUpdatePostDateStruct': {'date': '2022-06-09', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-03-09', 'studyFirstPostDateStruct': {'date': '2017-02-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2022-06-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-05-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Correlation Between Ploidy Status With Local Recurrence of Cancer', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer'}, {'measure': 'Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.'}], 'secondaryOutcomes': [{'measure': 'Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival'}, {'measure': 'Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer', 'timeFrame': 'a minimum of 6 months after surgery', 'description': 'Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Early rectal cancer', 'Ploidy', 'Tumour:stroma ratio'], 'conditions': ['Rectal Cancer']}, 'referencesModule': {'references': [{'pmid': '19224520', 'type': 'BACKGROUND', 'citation': 'Bach SP, Hill J, Monson JR, Simson JN, Lane L, Merrie A, Warren B, Mortensen NJ; Association of Coloproctology of Great Britain and Ireland Transanal Endoscopic Microsurgery (TEM) Collaboration. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg. 2009 Mar;96(3):280-90. doi: 10.1002/bjs.6456.'}, {'pmid': '3598327', 'type': 'BACKGROUND', 'citation': 'Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JM. Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis. Int J Colorectal Dis. 1987 Feb;2(1):17-21. doi: 10.1007/BF01648992.'}, {'pmid': '14504048', 'type': 'BACKGROUND', 'citation': 'Kristensen GB, Kildal W, Abeler VM, Kaern J, Vergote I, Trope CG, Danielsen HE. Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer. Ann Oncol. 2003 Oct;14(10):1494-500. doi: 10.1093/annonc/mdg403.'}, {'pmid': '24458470', 'type': 'BACKGROUND', 'citation': 'Park JH, Richards CH, McMillan DC, Horgan PG, Roxburgh CSD. The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014 Mar;25(3):644-651. doi: 10.1093/annonc/mdt593. Epub 2014 Jan 23.'}, {'pmid': '24548861', 'type': 'BACKGROUND', 'citation': 'Downey CL, Simpkins SA, White J, Holliday DL, Jones JL, Jordan LB, Kulka J, Pollock S, Rajan SS, Thygesen HH, Hanby AM, Speirs V. The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014 Apr 2;110(7):1744-7. doi: 10.1038/bjc.2014.69. Epub 2014 Feb 18.'}, {'pmid': '20407439', 'type': 'BACKGROUND', 'citation': 'West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010 May 11;102(10):1519-23. doi: 10.1038/sj.bjc.6605674. Epub 2010 Apr 20.'}]}, 'descriptionModule': {'briefSummary': 'Early rectal cancer can be removed by minimally-invasive surgery, and the standard pathological assessment of the removed tumour gives valuable information about how advanced the tumour is. This gives an indication of how likely the cancer is to recur, so doctors and patient can decide on the most appropriate further treatment and follow-up. However there is still much uncertainty in these predictions about recurrence. This study will assess two further pathology tests, ploidy and stroma ratio in the tumour, by correlating the results with outcome. This will determine whether these two tests provide additional value in predicting outcome. If so, clinicians would be better able to advise patients with early rectal cancer about their prognosis and further management.', 'detailedDescription': 'Early rectal cancer can be removed by minimally-invasive surgery, and the standard pathological assessment of the removed tumour gives valuable information about how advanced the tumour is. This information is very important in indicating whether the cancer is likely to recur, and therefore in advising the patient after surgery whether further treatment is advisable, and if not, what is the most appropriate follow-up regime. However there is still a lot of uncertainty in these predictions about recurrence of the cancer, and better tests are being sought. This study aims to look at two further pathology tests, ploidy and stroma ratio in the tumour, and correlate these test results with outcome in patients who have had an early rectal cancer removed. This will allow the investigators to assess whether these two tests provide additional value in predicting outcome. If so, clinicians would be better able to advise patients with early rectal cancer about their prognosis and further management.\n\nRoutine histopathology analysis of a rectal cancer specimen removed at surgery includes assessment of tumour size, depth of invasion, vascular, lymphatic and perineural invasion, tumour involvement of resection margins and nodal involvement. This information is valuable in predicting outcome. For example, predicted rates of local recurrence at 36 months following local excision of rectal cancer by transanal endoscopic microsurgery (TEM) based on tumour size, depth of invasion and lymphatic invasion have been tabulated. However such models are not perfect, and leave room for improvement. Ploidy and stroma ratio are two further tests which have shown some promise in predicting outcome.\n\nPloidy refers to the number of sets of chromosomes in a cell nucleus. Most human cells are normally diploid, with two sets of 23 chromosomes. Abnormal tumour cells may have a different number of sets of chromosomes, or be aneuploid, having some replicated or deleted chromosomes. In general, aneuploidy in cancer cells is associated with a worse prognosis. An early study of DNA ploidy in rectal cancer using flow cytometry showed an independent but small predictive effective of aneuploidy on survival. Technological advances now allow more accurate and detailed assessment of ploidy. The DNA ploidy status of tumour cells in early ovarian cancer has been found to predict which patients will benefit from adjuvant chemotherapy after surgery to remove the ovarian tumour and is used routinely in some centres to aid in decision-making.\n\nStroma ratio refers to the tumour: stroma ratio. A lower proportion of tumour cells or, conversely, a higher percentage of stroma, in a cancer tends to be associated with a poorer prognosis. This ratio has been found to be strongly associated with tumour growth and invasion in colorectal cancers, and to independently predict survival in patients undergoing surgery to removal colorectal tumours. However previous studies have looked mainly at more advanced colon cancers, rather than early rectal cancers, and have used only cancer-related death as the endpoint, rather than looking at local recurrence and response to adjuvant treatments.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Participants diagnosed with rectal cancer that is operable and patients who have already had rectal cancer removed by transanal endoscopic microsurgery (TEM) in Oxford since 2007.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participant is willing and able to give informed consent (in English) for participation in the study, or gave informed consent for donation of tissue for research at the time of surgery\n* Male or Female, aged 18 years or above\n* Diagnosed with operable rectal cancer\n* Due to undergo, or has already undergone, TEM surgery to remove rectal cancer\n* A useable tissue sample has already been, or will be, taken as part of routine surgery\n\nExclusion Criteria:\n\n* Age less than 18\n* Adults who are not able to give consent or who are deemed vulnerable\n* Participants who do not have a useable tissue sample will be excluded'}, 'identificationModule': {'nctId': 'NCT03039595', 'briefTitle': 'Ploidy and Stroma in Early Rectal Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Oxford University Hospitals NHS Trust'}, 'officialTitle': 'An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer', 'orgStudyIdInfo': {'id': '11846'}}, 'armsInterventionsModule': {'interventions': [{'name': 'Ploidy and tumour:stromal ratio measurements', 'type': 'OTHER', 'description': 'Ploidy and tumour:stromal ratio measurements will be made on specimens of early rectal cancer removed by transanal endoscopic microsurgery (TEM)'}]}, 'contactsLocationsModule': {'locations': [{'zip': 'OX3 7LE', 'city': 'Oxford', 'country': 'United Kingdom', 'facility': 'Churchill Hospital', 'geoPoint': {'lat': 51.75222, 'lon': -1.25596}}], 'overallOfficials': [{'name': 'Chris Cunningham, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Employee'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'No individual data will be made available'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oxford University Hospitals NHS Trust', 'class': 'OTHER'}, 'collaborators': [{'name': 'Oslo University Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Consultant colorectal surgeon', 'investigatorFullName': 'Chris Cunningham', 'investigatorAffiliation': 'Oxford University Hospitals NHS Trust'}}}}