PRecISion Medicine for Children With Cancer

Study Overview
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Brief Summary
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This is a multicentre prospective study of the feasibility and clinical value of a diagnostic service for identifying therapeutic targets and recommending personalised treatment for children and adolescents with high-risk cancer.

Detailed Description
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This is a multicentre study conducted under the Zero Childhood Cancer Program. The study will be enrolling patients under the age of 21 with high-risk cancer over 3 years from cancer centres in Australia. Patient's cancer cells will be tested for genetic abnormalities (mutations) and undergoing drug testing in highly specialised laboratories. A Multidisciplinary Tumour Board comprising of oncologists, clinical geneticists and scientists will then discuss the results of each case and determine whether a personalised medicine recommendation can be made. A report describing the results and Tumour Board recommendation (if any) will be provided to the patient's treating doctor. It is always at the discretion of the treating doctor whether to alter the patient's management based on the information arising from this research project.

Official Title
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A Multicenter Prospective Study of the Feasibility and Clinical Value of a Diagnostic Service for Identifying Therapeutic Targets and Recommending Personalised Treatment for Children and Adolescents With High-risk Cancer

Conditions
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Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor, Childhood Leukemia, Refractory Cancer, Relapsed Cancer

Intervention / Treatment
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* Diagnostic Test: Molecular profiling and drug testing


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (all must be met) Age ≤ 21 years Histologic diagnosis of high-risk malignancy defined as expected overall survival < 30% OR where standard therapy would result in unacceptable and severe morbidity Appropriate tissue samples are available for analysis Life expectancy > 6 weeks Written informed consent

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High-risk childhood cancers<br>Expected survival < 30% | Diagnostic Test: Molecular profiling and drug testing<br>* Laboratory analysis including: A. Tumour molecular profiling: targeted whole exon variant analysis, whole genome (DNA) and transcriptome (RNA) sequencing, methylation analysis, proteomics analysis, immunohistochemistry B. In vitro high-throughput drug sensitivity testing C. In vivo drug testing using patient-derived xenograft (PDX) models D. Liquid biopsies Multi-disciplinary Tumour Board case discussion Recommendation of personalised therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Personalized medicine recommendation | Proportion of patients for whom personalized medicine recommendation can be made using a comprehensive diagnostic platform within a clinically relevant timeframe | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor samples with actionable molecular alterations | Proportion of tumor samples found to have actionable molecular alterations | 5 years | 
| Successfully conducted in vitro high throughput drug screening and in vivo drug sensitivity testing | Proportion of tumours where in vitro high throughput drug screening and in vivo drug sensitivity testing can be successfully performed | 5 years | 
| Identification of potential treatment by in vitro or in vivo drug screening | Proportion of tumors for which a potential treatment option is identified by in vitro or in vivo drug screening | 5 years | 
| Reporting turnaround time | Number of weeks from enrollment to issuing a report to the treating clinician | 5 years | 
| Patients receiving the recommended personalized therapy | Proportion of patients who subsequently receive the recommended personalized therapy | 5 years | 
| Barriers or reasons for patients not receiving the recommended personalized therapy | Description of the barriers or reasons for patients not receiving the recommended personalized therapy | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, precision medicine, personalised medicine, high-risk cancer, refractory, recurrent, sequencing, patient derived xenograft, molecular profiling, paediatric