Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05252819 |
| Other study ID # |
21062 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 17, 2022 |
| Est. completion date |
November 30, 2023 |
Study information
| Verified date |
February 2024 |
| Source |
University of Nottingham |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Ataxia Telangiectasia (A-T) is an inherited disorder characterised by cerebellar
neurodegeneration, immunodeficiency and respiratory disease. People with A-T have abnormal
DNA repair and consequently have an increased risk of cancer. Despite this, current
guidelines for management of children and young people with A-T do not include cancer
surveillance.
Improvements in MRI technology have allowed whole-body MRI (WB-MRI) scanning with relatively
short acquisition times. Currently, WB-MRI protocols are used for diagnosing and monitoring
some primary and secondary cancers, including cancer surveillance in people with the
Li-Fraumeni syndrome, which is another genetic cancer predisposition syndrome. Therefore, the
research team believe that whole-body MRI provides a safe method for cancer surveillance in
children and young people with A-T. However, the investigators do not know whether cancer
surveillance in children and young people with A-T using whole-body MRI is feasible and
desirable.
The research team proposes a feasibility study of MRI-based cancer surveillance with
qualitative evaluation of participant experience with the primary aim to establish:
- feasibility of whole-body MRI for cancer surveillance in children and young people with
A-T
- views of, and psychological impact on, participants and families / carers participating
in whole-body MRI for cancer surveillance.
- feasibility of conducting a formal screening trial in terms of statistical design,
sample size, screening interval, comparator arms and international collaboration
Completion of this study will provide us with evidence of technical feasibility, very
strong evidence of child / family views, a viable formal screening trial design and an
engaged international research community, allowing us to proceed to a formal trial
establishing the efficacy of a cancer surveillance programme for children and young
people with A-T.
Description:
Ataxia Telangiectasia (A-T) is an autosomal recessive disorder characterised with cerebellar
neurodegeneration, immunodeficiency, respiratory disease and cancer susceptibility (22% by
age 20). A-T is a complex disorder caused by mutations in the Ataxia Telangiectasia Mutated
(ATM) gene which creates highly unstable ATM protein fragments. In the classical clinical
presentation of A-T there is no kinase activity due to the absence of ATM protein. One
consequence of this is that cellular DNA-repair pathways are compromised which allows breaks
in DNA strands leading to genomic instability and/or cell death. As a result, there is an
increase sensitivity to ionizing radiation and elevated cancer risk. Children less than 16
years with classical A-T demonstrate a predisposition to the development of different types
of lymphoid cancers (lymphoma and leukaemia). However non-lymphoid tumours can also occur.
The current practice at the United Kingdom Paediatric A-T clinic for cancer surveillance is
to perform blood testing, including full blood account, liver function tests and measurement
of circulating tumour marker Alpha-fetoprotein. Full blood account can detect an increase
white cell count and abnormal white cell populations and therefore, is effective in detecting
most types of leukaemia. Elevation of Alpha-Fetoprotein can be a marker of different types of
tumours, for example hepatocellular carcinoma and liver metastases, however is also often
elevated in people with A-T. Therefore, its use for detecting cancer in A-T is uncertain and
not currently evidence-based. The lack of evidence-based guidelines regarding the optimal
cancer surveillance strategy in children with A-T could delay the diagnosis and consequently
the treatment plan.
Magnetic Resonance Imaging (MRI) technology has progress rapidly since its discovery, making
it possible currently to perform whole-body MRI scans with relatively short acquisition
times. Presently, whole-body MRI protocols that include diffusion-weighted imaging and
structural (T1/Dixon) acquisitions are used for diagnosing and monitoring cancers (sarcomas,
metastases and haematological tumours like myeloma). A further advantage of this technique
compared to computed tomography is that does not involve radiation, which is important given
the elevated radiosensitivity of people with A-T.
The value of whole-body MRI in people with cancer predisposition has been shown in
Li-Fraumeni syndrome, syndrome that, like A-T, is associated with increased risk of
haematological and solid tumours. Despite the successful results of using a multimodality
protocol for cancer surveillance in Li-Fraumeni syndrome, it cannot be assumed that the
results will be the same in people with A-T as the also have respiratory and neurological
dysfunction that could influence the tolerability and image quality of the MRI scans. Also,
the profile of the tumours differs between these two syndromes. To date, the value of
whole-body MRI for cancer surveillance in children and young people with A-T has not been
demonstrated. It is unknown whether is possible to obtain diagnostic images, and the spectrum
of findings (both cancer and non-cancer) that can be detected has not been reported.
In addition to technical considerations, it is vital to understand the perspectives of people
affected by A-T regarding cancer surveillance. Participation in a cancer surveillance
programme could increase anxiety for both the participant and family, and it is possible that
negative psychological aspects could outweigh the perceived benefits or earlier cancer
detection. Compared to other screening programmes, it should be noted that these families are
already having to deal with a family member with complex progressive chronic disease, and so
emotional and psychological capacity to deal with added anxiety may be limited. Hence, it is
important to know, before conducting a full scale trial that will inform the current lack of
evidence-based guidelines, whether cancer surveillance in children and young people with A-T
using whole-body MRI is feasible and desirable.
