To improve outcomes for childhood cancer patients through the implementation of precision medicine.
Age < 18 years Note: Individual patients aged 19 - 25 years old with a pediatric cancer, e.g., neuroblastoma, may be enrolled after discussion with, and at the discretion of, the Study Chair or their delegate.
Life expectancy >6 weeks at time of enrolment
Consent i. Signed and dated informed consent for study enrolment from participant aged ≥ 18 years or from parent/guardian of participant aged <18 years. ii. Separate signed and dated informed consent for understanding the role of germline testing and choice for the return of germline results.
None
Patients \<18 years of age with a diagnosis of tumor or cancer Patients aged 19 - 25 years with a diagnosis of a pediatric tumor or cancer
Cohort
Prospective
Whole Genome Sequencing
GeneticEach tumor sample will be sequenced and analyzed in parallel with its matched normal (germline DNA from the same patient) to enable the identification of somatic aberrations.
RNA seq
GeneticResults will be used for bioinformatics analysis for fusion transcripts and gene expression.
DNA Methylation
GeneticGenome-wide assessment of DNA methylation will be conducted on all samples where possible.
Targeted Panel Sequencing
GeneticTargeted panel sequencing may be performed: 1. When WGS is not feasible or appropriate, e.g., insufficient DNA from fresh or frozen sample or only Formalin-Fixed Paraffin-Embedded (FFPE) material is available 2. When mosaicism is suspected 3. When indicated for a disease type
High Throughput Sequencing (in vitro)
GeneticHigh throughput drug screening will be attempted for tumors from Cohort 1 (high-risk cancers with survival \<30%) and selected tumor types.
Patient Derived Xenograft (PDX)(in vivo)
GeneticIn vivo drug testing in patient derived xenograft (PDX) will be attempted for tumors from Cohort 1 (high-risk cancers) and selected tumor types.
Liquid Biopsy
Other interventionLiquid biopsy will be investigated as a non-invasive method for diagnosis of tumors that are difficult to biopsy directly, understanding tumor heterogeneity, monitoring of treatment response, and detection of minimal residual disease (MRD)/relapse in leukemia, solid and CNS tumors.
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Treatment groupsSee each treatment group below.
Utility of recommended personalized therapy for HR childhood cancer patients.
Disease control rate (stable disease + partial response + complete response) in HR patients who have received recommended personalized therapy which are molecularly and/or preclinically directed
Utility of recommended personalized therapy for non-HR childhood cancer patients.
The proportion of non-HR patients for whom the disease specific, clinically relevant, virtual molecular panel provides additional or equivalent results for diagnosis and risk stratification when compared with routine diagnostic tests.
Utility of pre-defined virtual molecular panel for non-HR childhood cancer patients.
The proportion of non-HR patients for whom a pre-defined virtual molecular panel; leads to a streamline molecular report issued within 4 weeks from receipt of samples, changes or refines the initial histopathological diagnosis, changes or refines risk stratification at diagnosis, changes or refines treatment at diagnosis and/or facilitates enrolment in clinical trials requiring prior molecular studies.
Utility of comprehensive precision medicine for patients with rare tumors in childhood.
Proportion of rare cancer cohort patients for which comprehensive precision medicine improves diagnosis, identifies at least one therapeutic target or facilitates improvement in therapy within a clinically relevant timeframe.
Utility of Molecular Tumour Board (MTB) recommendation tier system for HR childhood cancer patients.
Evaluation of the correlation of MTB recommendation tier to treatment outcome, clinician rated value of MTB recommendation tier in facilitating therapeutic decision and drug access and proportion of HR patients for which the MTB recommendation improves diagnosis, risk stratification or facilitates improvement in therapy within a clinically relevant timeframe.
Utility of preclinical testing in HR childhood cancer patients.
Evaluation of proportion of tumors where in vitro sensitivity testing can be successfully performed compared with PRISM trial, turnaround time for preclinical in vitro and in vivo drug testing, proportion of tumors where in vitro drug sensitivity identifies additional molecular drivers and proportion of patients for whom preclinical testing: i. Facilitates therapeutic decision ii. Identifies additional therapeutic options in patients for whom genomic profiling did not identify molecular targets iii. Predicts clinical outcome
Click on the lead sponsor to view all of their trials.
Australian & New Zealand Children's Haematology/Oncology Group
Lead sponsor
Children's Cancer Institute (CCI)
Collaborator
Minderoo Foundation
Collaborator
Medical Research Future Fund
Collaborator
