Anal CancerNCT05835960
Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma
An observational study of Anal Cancer and Anal Squamous Intraepithelial Neoplasia, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This is a study involving exome sequencing and immune profiling of matched tissue and blood samples from patients with both high-grade squamous intraepithelial lesions and anal squamous cell carcinoma. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Anal Cancer, Anal Squamous Intraepithelial Neoplasia
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2019to 1 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with HPV driven AIN 3 and anal SCC.
Who may be able to join
- Males or females, with or without HIV over the age of 18 years at the time of recruitment.
- Patients with either:
- A previous complete set of formalin fixed tissue samples of all stages of AIN and anal SCC.
- A new diagnosis of AIN3 and are about to undergo Anal mapping.
- A new diagnosis of Anal Squamous Cell Carcinoma and are about to undergo an Examination under Anaesthetic.
Who cannot join
- Patients without mental capacity to consent.
- Patients less than 18 years old.
- Patients with anal pathology which is not HPV driven AIN/SCC.
Trial locations and contacts
1 site in 1 country.
Christos Kontovounisios, MD, PhD, FACS, FRCS contact
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College London- Chelsea and Westminster NHS Foundation Trust
London, SW10 9NH
Micol Lupi, 020 3315 8000 ext. 4469, m.lupi22@imperial.ac.uk
Christos Kontovounisios, 020 3315 8000 ext. 4469, c.kontovounisios@imperial.ac.uk
About this study
Official title: The Role of Early Diagnosis and Treatment of Anal Intraepithelial Neoplasia in the Prevention of Anal Squamous Cell Carcinoma: Identifying Prognostic Biomarkers.
This is a study involving exome sequencing and immune profiling of matched tissue and blood samples from patients with both high-grade squamous intraepithelial lesions and anal squamous cell carcinoma. This is a collaborative project between Imperial College London and the Institute of Cancer Research (ICR), investigating the genetic predeterminants for the progression of anal HSIL to SCC as well as the immunogenetic profile of these conditions will be beneficial for risk stratification (with respect to identifying those individuals with anal HSIL most likely to progress to invasive disease), the identification of potential new drug targets and will add to our understanding of how the tumour microenvironment may influence treatment response and disease recurrence of both anal HSIL and SCC.
Read the detailed description
Patients, as identified by the colorectal MDT, are approached, and consented for tissue and blood collection on the day of their diagnostic procedure; the plasma and buffy coat are extracted from the EDTA tubes. A tissue biopsy is performed adjacent to the area sampled for diagnosis and flash frozen in liquid nitrogen. Once the diagnosis of anal cancer is confirmed, the FFPE diagnostic tissue, is requested from the Tissue Bank for the study.
The FFPE and the fresh frozen tissue samples are sliced and put on slides. Stained slides are reviewed by a consultant histopathologist, areas of anal HSIL and SCC are marked.
All samples are transferred to the ICR. Tumour DNA and RNA are extracted from the tissue samples and germline DNA from the buffy coat of the blood sample.
Exome sequencing followed by Bioinformatic analysis is carried out where somatic mutations are evaluated for impact on gene expression and compared between germline, anal HSIL and SCC samples. After a quality control process is complete, the entire dataset is compared with the germline DNA reads, thereby identifying somatic mutations. Candidate mutations are finally cross-referenced with the Cancer Genome Census and string analysis of relevant mutations is performed to assess for cancerogenic impact.
Bulk RNA and targeted RNA based T-Cell Receptor (TCR) sequencing will be carried out, with TCR sequencing also being performed on the blood. This will establish which immune cell types are present in the SCC vs HSIL (by transcriptomic deconvolution), and the repertoire of TCR in peripheral blood, HSIL and SCC. Multiplex immunofluorescence technology against distinct immune panels (established within the CTI), will further evaluate the SCC and HSIL immune microenvironments.
The immune-data will be linked to clinical outcome (both radiological and clinical), following radical chemoradiation.
- Keywords
- Anal Cancer, Early Diagnosis, Anal Squamous Intraepithelial Lesion, Biomarker, HPV, Treatment response
- Medical subject headings
- Anus Neoplasms, Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify prognostic biomarkers with respect to anal SCC disease progression and treatment response.
Genomic and immune biomarkers
Measured: 1 year
Establish the feasibility of immune analysis and NGS in informing patient treatment decisions.
Pilot study, with low patient numbers
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2023
- Study start1 Apr 2019
- Primary completion30 Apr 2024 (estimated)
- Study completion1 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05835960
- Sponsor's protocol ID
- 234715
- Status last verified
- Apr 2023
- First submitted
- 19 Apr 2023
- Last updated
- 28 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Early Diagnosis and Treatment of Anal Intraepithelial Neoplasia in the Prevention of Anal Squamous Cell Carcinoma: Identifying Prognostic Biomarkers.
- ClinicalTrials.gov ID
- NCT05835960
- Acronym / sponsor ID
- 234715
- Keywords
- Anal Cancer, Early Diagnosis, Anal Squamous Intraepithelial Lesion, Biomarker, HPV, Treatment response
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 30 Apr 2024 (estimated)
- Study completion
- 1 Oct 2024 (estimated)
- First posted
- 28 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study involving exome sequencing and immune profiling of matched tissue and blood samples from patients with both high-grade squamous intraepithelial lesions and anal squamous cell carcinoma. This is a collaborative project between Imperial College London and the Institute of Cancer Research (ICR), investigating the genetic predeterminants for the progression of anal HSIL to SCC as well as the immunogenetic profile of these conditions will be beneficial for risk stratification (with respect to identifying those individuals with anal HSIL most likely to progress to invasive disease), the identification of potential new drug targets and will add to our understanding of how the tumour microenvironment may influence treatment response and disease recurrence of both anal HSIL and SCC.
Detailed description
Patients, as identified by the colorectal MDT, are approached, and consented for tissue and blood collection on the day of their diagnostic procedure; the plasma and buffy coat are extracted from the EDTA tubes. A tissue biopsy is performed adjacent to the area sampled for diagnosis and flash frozen in liquid nitrogen. Once the diagnosis of anal cancer is confirmed, the FFPE diagnostic tissue, is requested from the Tissue Bank for the study.
The FFPE and the fresh frozen tissue samples are sliced and put on slides. Stained slides are reviewed by a consultant histopathologist, areas of anal HSIL and SCC are marked.
All samples are transferred to the ICR. Tumour DNA and RNA are extracted from the tissue samples and germline DNA from the buffy coat of the blood sample.
Exome sequencing followed by Bioinformatic analysis is carried out where somatic mutations are evaluated for impact on gene expression and compared between germline, anal HSIL and SCC samples. After a quality control process is complete, the entire dataset is compared with the germline DNA reads, thereby identifying somatic mutations. Candidate mutations are finally cross-referenced with the Cancer Genome Census and string analysis of relevant mutations is performed to assess for cancerogenic impact.
Bulk RNA and targeted RNA based T-Cell Receptor (TCR) sequencing will be carried out, with TCR sequencing also being performed on the blood. This will establish which immune cell types are present in the SCC vs HSIL (by transcriptomic deconvolution), and the repertoire of TCR in peripheral blood, HSIL and SCC. Multiplex immunofluorescence technology against distinct immune panels (established within the CTI), will further evaluate the SCC and HSIL immune microenvironments.
The immune-data will be linked to clinical outcome (both radiological and clinical), following radical chemoradiation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with HPV driven AIN 3 and anal SCC.
Key inclusion criteria (5 listed)
- Males or females, with or without HIV over the age of 18 years at the time of recruitment.
- A previous complete set of formalin fixed tissue samples of all stages of AIN and anal SCC.
- A new diagnosis of AIN3 and are about to undergo Anal mapping.
- A new diagnosis of Anal Squamous Cell Carcinoma and are about to undergo an Examination under Anaesthetic.
Key exclusion criteria (3 listed)
- Patients without mental capacity to consent.
- Patients less than 18 years old.
- Patients with anal pathology which is not HPV driven AIN/SCC.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identify prognostic biomarkers with respect to anal SCC disease progression and treatment response.
Time frame: 1 year
Genomic and immune biomarkers
Establish the feasibility of immune analysis and NGS in informing patient treatment decisions.
Time frame: 1 year
Pilot study, with low patient numbers
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2023.
Related trials for Anal Cancer
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
Study of Pembrolizumab, Carboplatin, Paclitaxel, and Radiation for the Treatment of Early-Stage Anal Cancer
Anal Cancer
Active, not recruitingPhase 2
Anti-PD-1 and mDCF Followed by Chemoradiotherapy in Patients With Stage III Squamous Cell Anal Carcinoma.
Squamous Cell Carcinoma of the Anus Stage III
Recruiting
Distance-Based Exercise to Preserve Function and Prevent Disability
Localized Malignant Solid Neoplasm, Anal Cancer
Active, not recruitingPhase 2
Combination of Spartalizumab, mDCF and Radiotherapy in Patients With Metastatic Squamous Cell Anal Carcinoma
Squamous Cell Anal Carcinoma, Metastatic Squamous Cell Carcinoma
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.
Christos Kontovounisios, MD, PhD, FACS, FRCS contact
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 Anal Cancer and Anal Squamous Intraepithelial Neoplasia, run by Imperial College London 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: status not confirmed, as of the sponsor's last update on 28 Apr 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Micol Lupi, BSc, MBBS, MRCS (020 3315 8000 ext. 4469, m.lupi22@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify prognostic biomarkers with respect to anal SCC disease progression and treatment response. (time frame: 1 year). 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?
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 28 Apr 2023.