Rectal CancerNCT03039595
Ploidy and Stroma in Early Rectal Cancer
An observational study of Rectal Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Ploidy and tumour:stromal ratio measurements
- How many people
- 150 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Mar 2017to 31 Jul 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
- Male or Female, aged 18 years or above
- Diagnosed with operable rectal cancer
- Due to undergo, or has already undergone, TEM surgery to remove rectal cancer
- A useable tissue sample has already been, or will be, taken as part of routine surgery
Who cannot join
- Age less than 18
- Adults who are not able to give consent or who are deemed vulnerable
- Participants who do not have a useable tissue sample will be excluded
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer
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.
Read the detailed description
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.
Routine 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.
Ploidy 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.
Stroma 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.
- Conditions
- Rectal Cancer
- Being tested
- Ploidy and tumour:stromal ratio measurements
- Keywords
- Early rectal cancer, Ploidy, Tumour:stroma ratio
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ploidy and tumour:stromal ratio measurementsOther
Ploidy and tumour:stromal ratio measurements will be made on specimens of early rectal cancer removed by transanal endoscopic microsurgery (TEM)
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Between Ploidy Status With Local Recurrence of Cancer
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
Measured: a minimum of 6 months after surgery
Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer
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.
Measured: a minimum of 6 months after surgery
Secondary outcomes (2)
Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer
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
Measured: a minimum of 6 months after surgery
Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer
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.
Measured: a minimum of 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start29 Mar 2017
- Primary completion31 May 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Oslo University Hospital
- Responsible party
- Principal investigator, Chris Cunningham, Oxford University Hospitals NHS Trust
- Investigators
- Chris Cunningham, MD, Principal investigator, Employee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03039595
- Sponsor's protocol ID
- 11846
- Status last verified
- Mar 2022
- First submitted
- 30 Jan 2017
- Last updated
- 9 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No individual data will be made available
Publications
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.
PubMed 19224520Goh 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.
PubMed 3598327Kristensen 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.
PubMed 14504048Park 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.
PubMed 24458470Downey 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.
PubMed 24548861West 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.
PubMed 20407439
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer
- ClinicalTrials.gov ID
- NCT03039595
- Acronym / sponsor ID
- 11846
- Conditions
- Rectal Cancer
- Keywords
- Early rectal cancer, Ploidy, Tumour:stroma ratio
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Oxford University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Oslo University Hospital
- Study start
- 29 Mar 2017 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 1 Feb 2017 (estimated)
- Results
- Posted 9 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Routine 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.
Ploidy 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.
Stroma 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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (5 listed)
- 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
- Male or Female, aged 18 years or above
- Diagnosed with operable rectal cancer
- Due to undergo, or has already undergone, TEM surgery to remove rectal cancer
- A useable tissue sample has already been, or will be, taken as part of routine surgery
Key exclusion criteria (3 listed)
- Age less than 18
- Adults who are not able to give consent or who are deemed vulnerable
- Participants who do not have a useable tissue sample will be excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ploidy and tumour:stromal ratio measurementsPloidy and tumour:stromal ratio measurements will be made on specimens of early rectal cancer removed by transanal endoscopic microsurgery (TEM) | Other | – |
Primary outcome
Correlation Between Ploidy Status With Local Recurrence of Cancer
Time frame: a minimum of 6 months after surgery
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
Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer
Time frame: a minimum of 6 months after surgery
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.
2 secondary outcomes
Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time frame: a minimum of 6 months after surgery
Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time frame: a minimum of 6 months after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19224520Bach 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.
- Background: PubMed 3598327Goh 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.
- Background: PubMed 14504048Kristensen 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.
- Background: PubMed 24458470Park 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.
- Background: PubMed 24548861Downey 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.
- Background: PubMed 20407439West 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.
- Individual participant dataSharing planned: No. No individual data will be made available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Cunningham, MD principal investigator
Employee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectal Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation Between Ploidy Status With Local Recurrence of Cancer (time frame: a minimum of 6 months after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03039595, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2022.