Clinical trial NCT04903782: Cancer Predisposition Testing by Family-based Whole-genome Sequencing (WGS) in Every Child With Newly Diagnosed Cancer
Official title: Assessment of the Utility of Family-based (Trio) Whole-genome Sequencing for Cancer Predisposition Testing in Sequential Newly Diagnosed Paediatric and Adolescent Cancer Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neoplastic Syndromes, Hereditary
Cancer
Genetic Predisposition to Disease
Keywords: Germ-line Mutation
Disease Susceptibility
Child
Pediatrics
Genomics
Next Generation Sequencing
Risk
Lead sponsor: Sydney Children's Hospitals Network
Sponsor class: OTHER
Collaborators: name: Children's Cancer Institute Australia
First posted: 2021-05-27
Enrollment: 270
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Paediatric patients who are being treated for a newly diagnosed cancer in New South Wales, Australia

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.

Eligibility criteria: * New diagnosis of malignancy
* Age ≤ 21 years
* Written informed consent

Psychosocial component:

* Participants (≥ 12 years)
* Parent/caregiver(s) of participants
* Healthcare professionals involved in the care of patients enrolled in the study

Primary outcomes:
measure: 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).
timeFrame: 2 years
Secondary outcomes:
measure: The proportion of individuals found to have a reportable germline mutation in a CPG
timeFrame: 2 years
measure: The proportion of patients who have de-novo vs. inherited mutation in CPG.
timeFrame: 2 years
measure: Turnaround time for issuing a report to the treating clinician.
timeFrame: 2 years
measure: The proportion of participants with a complete recording of family history of cancer.
timeFrame: 2 years
measure: Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.
timeFrame: 2 years
measure: The proportion of participants with CPS who undergo cancer surveillance.
timeFrame: 2 years
measure: Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.
timeFrame: 2 years
measure: The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents.
timeFrame: 5 years
measure: Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.
timeFrame: 5 years
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: John Hunter Children's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
Study officials:
References: