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

Assessment of the Utility of Family-based (Trio) Whole-genome Sequencing for Cancer Predisposition Testing in Sequential Newly Diagnosed Paediatric and Adolescent Cancer Patients

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 Overview

• Status: Recruiting
• Conditions: Cancer; Neoplastic Syndromes, Hereditary; Genetic Predisposition to Disease
• Intervention / Treatment: Diagnostic test: Family-based whole genome sequencing

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.

• Study Type: Observational
• Enrollment (Anticipated): 270

Contacts and Locations

• Study Contact: Name: Clinical Trials Manager; Phone Number: +61 2 9382 3122; Email: SCHN-PREDICT@health.nsw.gov.au

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • Recruiting
      • John Hunter Children's Hospital
      • Contact: Frank Alvaro
    • Sydney, New South Wales, Australia, 2031
      • Recruiting
      • Sydney Children's Hospital
      • Contact: Kathy Tucker
    • Sydney, New South Wales, Australia, 2145
      • Recruiting
      • The Children's Hospital at Westmead
      • Contact: Luciano Dalla-Pozza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Paediatric patients who are being treated for a newly diagnosed cancer in New South Wales, Australia

Description

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children and adolescents with newly diagnosed malignancy	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
The proportion of individuals found to have a reportable germline mutation in a CPG		2 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 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
Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.		2 years
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
Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.		5 years

Collaborators and Investigators

• Sponsor: Sydney Children's Hospitals Network
• Collaborators: Children's Cancer Institute Australia

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Anticipated): March 8, 2023
• Study Completion (Anticipated): June 15, 2028

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Child; Pediatrics; Genomics; Risk; Next Generation Sequencing; Germ-line Mutation; Disease Susceptibility
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Neoplasms; Disease Susceptibility; Genetic Predisposition to Disease; Neoplastic Syndromes, Hereditary
• Other Study ID Numbers: PREDICT (CardioDx)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No