Cancer Predisposition Testing by Family-based Whole-genome Sequencing (WGS) in Every Child With Newly Diagnosed Cancer

Cancer Clinical Trial

— PREDICT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04903782
• Other study ID #: PREDICT
• Status: Recruiting
• Start date: March 8, 2021
• Est. completion date: June 15, 2028

Study information

• Verified date: November 2022
• Source: Sydney Children's Hospitals Network
• Contact: Clinical Trials Manager
• Phone: +61 2 9382 3122
• Email: SCHN-PREDICT[@]health.nsw.gov.au
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: June 15, 2028
• Est. primary completion date: March 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Cancer
• Disease Susceptibility
• Genetic Predisposition to Disease
• Neoplasms
• Neoplastic Syndromes, Hereditary

Intervention

Diagnostic Test:
• Family-based whole genome sequencing
Germline whole-genome family-based sequencing and variant identification. Multidisciplinary Meeting case discussion. Recommendation of referral to a Cancer Genetics Clinic for further investigation, follow up and/or genetic counselling. Psychosocial study to analyse the impact of germline sequencing on families.

Locations

Country	Name	City	State
Australia	John Hunter Children's Hospital	Newcastle	New South Wales
Australia	Sydney Children's Hospital	Sydney	New South Wales
Australia	The Children's Hospital at Westmead	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Sydney Children's Hospitals Network	Children's Cancer Institute Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The proportion of individuals found to have a reportable germline mutation in a CPG		2 years
Secondary	The proportion of patients who have de-novo vs. inherited mutation in CPG.		2 years
Secondary	Turnaround time for issuing a report to the treating clinician.		2 years
Secondary	The proportion of participants with a complete recording of family history of cancer.		2 years
Secondary	Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.		2 years
Secondary	The proportion of participants with CPS who undergo cancer surveillance.		2 years
Secondary	Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.		2 years
Secondary	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
Secondary	Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.		2 years
Secondary	The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents.	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.	5 years
Secondary	Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.		5 years