Neoplastic Syndromes, HereditaryPREDICTNCT04903782
Cancer Predisposition Testing by Family-based Whole-genome Sequencing (WGS) in Every Child With Newly Diagnosed Cancer
An observational study of Neoplastic Syndromes, Hereditary and Cancer, run by Sydney Children's Hospitals Network at 3 sites in Australia.
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 Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neoplastic Syndromes, Hereditary, Cancer, Genetic Predisposition to Disease
- What is being tested?
- Family-based whole genome sequencing
- How many people
- 270 participants
- Where
- 3 sitesAustralia
- Study dates
- 8 Mar 2021to 15 Jun 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Paediatric patients who are being treated for a newly diagnosed cancer in New South Wales, Australia
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Australia3 sites, 3 recruiting
- Recruiting
John Hunter Children's Hospital
Newcastle, New South Wales, 2305
Frank Alvaro
- Recruiting
Sydney Children's Hospital
Sydney, New South Wales, 2031
Kathy Tucker
- Recruiting
The Children's Hospital at Westmead
Sydney, New South Wales, 2145
Luciano Dalla-Pozza
About this study
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
Assessment of the utility of family-based (trio) whole-genome sequencing for cancer predisposition testing in sequential newly diagnosed paediatric and adolescent cancer patients
Read the 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.
- Being tested
- Family-based whole genome sequencing
- Keywords
- Germ-line Mutation, Disease Susceptibility, Child, Pediatrics, Genomics, Next Generation Sequencing, Risk
- Medical subject headings
- Neoplastic Syndromes, Hereditary, Neoplasms, Genetic Predisposition to Disease, Disease Susceptibility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Family-based whole genome sequencingDiagnostic test
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Children and adolescents with newly diagnosed malignancy | Not described Receives: Diagnostic Test: Family-based whole genome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 years
Secondary outcomes (11)
The proportion of individuals found to have a reportable germline mutation in a CPG
Measured: 2 years
The proportion of patients who have de-novo vs. inherited mutation in CPG.
Measured: 2 years
Turnaround time for issuing a report to the treating clinician.
Measured: 2 years
The proportion of participants with a complete recording of family history of cancer.
Measured: 2 years
Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.
Measured: 2 years
The proportion of participants with CPS who undergo cancer surveillance.
Measured: 2 years
Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.
Measured: 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.
Measured: 2 years
Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.
Measured: 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.
Measured: 5 years
Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2021
- Study start8 Mar 2021
- Primary completion8 Mar 2023 (estimated)
- Study completion15 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplastic Syndromes, HereditaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sydney Children's Hospitals Network
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Cancer Institute Australia
- Responsible party
- Principal investigator, Kathy Tucker, Sydney Children's Hospitals Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04903782
- Sponsor's protocol ID
- PREDICT
- Acronym
- PREDICT
- Status last verified
- Nov 2022
- First submitted
- 16 Mar 2021
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fuentes Bolanos NA, Padhye B, Daley M, Hunter J, Hetherington K, Warby M, Courtney E, Kirk J, Josephi-Taylor S, Chen Y, Alvaro F, Barlow-Stewart K, Wong-Erasmus M, Barahona P, Ajuyah P, Altekoester AK, Tyrrell VJ, Lau LMS, Wakefield C, Sylvester D, Tucker K, Pinese M, Dalla Pozza L, O'Brien TA. Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study. BMJ Open. 2023 May 30;13(5):e070082. doi: 10.1136/bmjopen-2022-070082.
PubMed 37253493
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04903782
- Acronym / sponsor ID
- PREDICT / PREDICT
- Keywords
- Germ-line Mutation, Disease Susceptibility, Child, Pediatrics, Genomics, Next Generation Sequencing, Risk
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Sydney Children's Hospitals NetworkUniversity, hospital or other
- Collaborators
- Children's Cancer Institute Australia
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 8 Mar 2023 (estimated)
- Study completion
- 15 Jun 2028 (estimated)
- First posted
- 27 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children and adolescents with newly diagnosed malignancy | – | Diagnostic Test: Family-based whole genome sequencing |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Paediatric patients who are being treated for a newly diagnosed cancer in New South Wales, Australia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Family-based whole genome sequencing1. Germline whole-genome family-based sequencing and variant identification. 2. Multidisciplinary Meeting case discussion. 3. Recommendation of referral to a Cancer Genetics Clinic for further investigation, follow up and/or genetic counselling. 4. Psychosocial study to analyse the impact of germline sequencing on families. | Diagnostic test | Children and adolescents with newly diagnosed malignancy |
Primary outcome
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).
Time frame: 2 years
11 secondary outcomes
The proportion of individuals found to have a reportable germline mutation in a CPG
Time frame: 2 years
The proportion of patients who have de-novo vs. inherited mutation in CPG.
Time frame: 2 years
Turnaround time for issuing a report to the treating clinician.
Time frame: 2 years
The proportion of participants with a complete recording of family history of cancer.
Time frame: 2 years
Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.
Time frame: 2 years
The proportion of participants with CPS who undergo cancer surveillance.
Time frame: 2 years
Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.
Time frame: 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.
Time frame: 2 years
Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.
Time frame: 2 years
The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents.
Time frame: 5 years
Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Derived from this study: PubMed 37253493Fuentes Bolanos NA, Padhye B, Daley M, Hunter J, Hetherington K, Warby M, Courtney E, Kirk J, Josephi-Taylor S, Chen Y, Alvaro F, Barlow-Stewart K, Wong-Erasmus M, Barahona P, Ajuyah P, Altekoester AK, Tyrrell VJ, Lau LMS, Wakefield C, Sylvester D, Tucker K, Pinese M, Dalla Pozza L, O'Brien TA. Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study. BMJ Open. 2023 May 30;13(5):e070082. doi: 10.1136/bmjopen-2022-070082.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neoplastic Syndromes, Hereditary and Cancer, run by Sydney Children's Hospitals Network at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Manager (+61 2 9382 3122, SCHN-PREDICT@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04903782, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.