Cancer Predisposition Testing by Family-based Whole-genome Sequencing (WGS) in Every Child With Newly Diagnosed Cancer
- Conditions
- Neoplastic Syndromes, HereditaryCancerGenetic Predisposition to Disease
- Interventions
- Diagnostic Test: Family-based whole genome sequencing
- Registration Number
- NCT04903782
- Lead Sponsor
- Sydney Children's Hospitals Network
- Brief Summary
Assessment of the utility of family-based (trio) whole-genome sequencing for cancer predisposition testing in sequential newly diagnosed paediatric and adolescent cancer patients
- Detailed Description
Cancer Predisposition Syndromes (CPS), caused by germline mutations in cancer predisposition genes (CPG) are heritable disorders associated with an increased risk of developing certain types of cancer.
Knowledge of CPG will advance the understanding of tumorigenesis, improve patient care, and facilitate genetic counselling of patients and families. But the prevalence of CPS in Australian children with cancer and the psychosocial impact of germline sequencing to identify CPG have not been studied.
The clinical benefit of family-based WGS in every new child with cancer compared with conventional predictive factors is currently unknown. By testing every child with newly diagnosed cancer the aim is to determine the utility of this approach and its impact on participants and families.
The principal objective of the proposed multicentre prospective study is establish the clinical benefit and utility of family-based WGS to identify underlying CPS in every newly diagnosed child with cancer.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 270
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Children and adolescents with newly diagnosed malignancy Family-based whole genome sequencing -
- Primary Outcome Measures
Name Time Method The proportion of patients with CPS identify by WGS as compared to those correctly identified by clinical information (i.e. family history, tumour type, physical findings). 2 years
- Secondary Outcome Measures
Name Time Method Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer. 2 years Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer. 5 years The proportion of patients who have de-novo vs. inherited mutation in CPG. 2 years Turnaround time for issuing a report to the treating clinician. 2 years The proportion of participants with a complete recording of family history of cancer. 2 years Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors. 2 years The proportion of individuals found to have a reportable germline mutation in a CPG 2 years The proportion of participants with CPS who undergo cancer surveillance. 2 years Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence. 2 years Quantify the frequency of rare noncoding, complex, and oligogenic variation (in units of variants/person, and genes with variants/person), as detected by WGS, in a paediatric cancer population relative to cancer-free parents and population controls. 2 years The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents. 5 years This will be achieved through identifying the incidence of patients and parents enrolled in the study experiencing clinically significant levels of distress, defined as a \>7 rating on any of the outcome measures in the Emotion Thermometers Tool©. The incidence of parents and patients experiencing other psychological outcomes such as reduced quality of life will also be identified using the validated scales EuroQoL EQ-5D-5L (parent proxy)/EQ-5D-Y (youth version), Decisional Regret Scale and the Trust In Physician Scale (adapted for a paediatric setting). Psychological outcomes will be re-assessed over the 5 year course of the study to assess impacts of germline sequencing over time.
Trial Locations
- Locations (3)
Sydney Children's Hospital
🇦🇺Sydney, New South Wales, Australia
The Children's Hospital at Westmead
🇦🇺Sydney, New South Wales, Australia
John Hunter Children's Hospital
🇦🇺Newcastle, New South Wales, Australia