Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04601727 |
| Other study ID # |
2-014-20 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2020 |
| Est. completion date |
May 16, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
University of Aberdeen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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.
Description:
Introduction:
Pelvic 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.
Understanding 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.
Clinical 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.
This 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
Study design:
Patients 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.
The 1st step for eligible patients is allocation to a consultant colorectal surgeon, who will
meet the patient to confirm the standard plan for treatment.
The 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.
Pelvic 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.
Step 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.
The 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.
Step 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.
Step 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.
Step 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
There 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.
The 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.
