Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05539638 |
| Other study ID # |
AC21058 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 14, 2022 |
| Est. completion date |
August 31, 2027 |
Study information
| Verified date |
January 2024 |
| Source |
University of Edinburgh |
| Contact |
Iain Nixon |
| Phone |
07968498525 |
| Email |
Iain.Nixon[@]nhslothian.scot.nhs.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Cancers of the throat, oropharyngeal squamous cell carcinoma (OPSCC), are highly prevalent
across Scotland. Over the past 10 years, both global and Scottish cases of OPSCC have
increased, particularly those associated with human papillomavirus (HPV). However there has
been little change in techniques for diagnosis and monitoring. Although imaging technologies
are improving, results of imaging are often indeterminate and clinicians require additional
tools to make informed decisions. With this in mind our research team have established a
range of blood- based tests which detect and monitor cancer DNA fragments shed by tumours
into the blood stream in OPSCC patients. Our initial studies have shown that such tests,
which are minimally invasive compared to surgical biopsy, hold the potential to provide an
accurate, "real-time" method to monitor patient response to treatment, identify early relapse
and assist in clinical decision making. The investigators aim to expand these results to
assist clinical decisions for both virally associated and non-viral associated OPSCC.
Following this, the investigators will focus on the poorest prognosis OPSCC group (non-HPV
tumours) by applying state-of-the-art DNA detection and sequencing technologies to analyse
tumour- derived DNA fragments in the bloodstream, to follow treatment response and to develop
new methods for detecting relapse and resistance to treatment in OPSCC. Ultimately, the
investigators envisage that the implementation of such genetic assays of tumours and the
fragments that they release into the bloodstream will provide a transformative shift in the
clinical assessment and quality of life of OPSCC patients in Scotland.
Description:
Oropharyngeal squamous cell carcinoma (OPSCC) is an increasingly prevalent cancer type in
Scotland, with an annual incidence rate of 23.4 per 100,000 of population in 2017 compared to
17.3 per 100,000 in 1993 [1]. This is due in part to an increased frequency of human
papillomavirus (HPV) -related disease, which accounts for >70% of cases of OPSCC, and to
continuing high rates of smoking. The current standard of care in OPSCC rests on clinical
assessment and cross-sectional imaging followed by biopsy with histopathological diagnosis
via immunohistochemistry (IHC) and PCR testing of the tumour for HPV. Follow-up is by
chemo-radiotherapy (CRT) in most cases, with interval imaging to gauge post-treatment
response to therapy and salvage surgery as required [2]. HPV+ve OPSCC has a generally good
prognosis after treatment with CRT (3-year survival 82%), whilst HPV-ve OPSCC has a much
poorer prognosis (3-year survival 57%)[3]. Surgical access to post-treatment OPSCC for biopsy
can be difficult and even with recent advances in functional imaging there are still
significant numbers of patients, at first presentation and at relapse, with indeterminate
results [4]. The poor prognosis of HPV-ve disease and the major differences in prognosis and
management between HPV+ve and -ve disease underline the importance of accurate identification
of HPV status in patients with OPSCC and emphasise the need for more reliable markers of
residual or recurrent disease.
The analysis of circulating tumour-derived DNA (ctDNA) from patient blood - "liquid biopsy" -
represents a minimally invasive approach to cancer diagnosis and management, with the
potential to transform clinical care through identification in blood ctDNA of actionable
tumour-derived mutations, detection of minimal residual disease and early detection of
disease recurrence [5]. There has been significant interest in developing liquid biopsy
approaches in HPV+ve OPSCC, with several studies including our own indicating that real-time
monitoring of HPV levels in plasma cell-free DNA (cfDNA) can accurately determine HPV status,
indicate completeness of response to treatment and provide evidence of tumour recurrence
earlier than routine surveillance and before symptomatic presentation [6-8] (Thomson et al
2020, MedRxiv). In HPV-ve OPSCC, a particular problem in Scotland due to high rates of
smoking, no such blood-based markers are available. As well as the opportunities to validate
and translate HPV cfDNA as a biomarker for remission and relapse in HPV+ve OPSCC, there is
therefore a need to develop new diagnostic assays to assist clinical decision-making steps in
the management of HPV-ve disease.
The investigators aim to carry out liquid biopsy studies that will improve diagnostic
accuracy and clinical management of Scottish OPSCC patients. In HPV+ve OPSCC, The
investigators will expand our existing cohort and prospectively evaluate the clinical utility
of cfDNA HPV analysis as a biomarker for routine care. In HPV-ve patients, The investigators
will study the development and evolution of HPV-ve disease through combined genomic analyses
of tumour DNA and circulating cfDNA, with the aim of identifying blood-based biomarkers and
new targets for personalised therapy in this poor prognosis form of OPSCC. Understanding the
molecular events surrounding OPSCC development and responsiveness to treatment, and
identifying biomarkers for blood-based disease monitoring stand to have a significant impact
on patient survival and quality of life of Scottish patients with OPSCC. The work proposed
here - built upon a strong foundation of pilot data and collaboration between academia and
the NHS - will directly assist clinical care and treatment efficacy for OPSCC patients in
Scotland.
