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

Sponsor

Sydney Children's Hospitals Network (Other)

Overall Status

Recruiting

CT.gov ID

NCT04903782

Collaborator

Children's Cancer Institute Australia (Other)

270

Enrollment

Locations

87.3

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Neoplastic Syndromes, Hereditary Cancer Genetic Predisposition to Disease	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 Design

Study Type:

Observational

Anticipated Enrollment :

270 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Mar 8, 2021

Anticipated Primary Completion Date :

Mar 8, 2023

Anticipated Study Completion Date :

Jun 15, 2028

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

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

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. [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.
Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer. [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Hunter Children's Hospital	Newcastle	New South Wales	Australia	2305
2	Sydney Children's Hospital	Sydney	New South Wales	Australia	2031
3	The Children's Hospital at Westmead	Sydney	New South Wales	Australia	2145