Childhood Brain Tumor, Childhood Cancer, Childhood Leukemia, Childhood Solid Tumor, Refractory Cancer, Relapsed Cancer
Conditions
Keywords
children, precision medicine, personalised medicine, high-risk cancer, refractory, recurrent, sequencing, patient derived xenograft, molecular profiling, paediatric
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTMolecular profiling and drug testing
1. 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 2. Multi-disciplinary Tumour Board case discussion 3. Recommendation of personalised therapy
Sponsors
Children's Cancer Institute Australia
Australian & New Zealand Children's Haematology/Oncology Group
Garvan Institute of Medical Research
German Cancer Research Center
Sydney Children's Hospitals Network
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
(all must be met) 1. Age ≤ 21 years 2. Histologic diagnosis of high-risk malignancy defined as expected overall survival \< 30% OR where standard therapy would result in unacceptable and severe morbidity 3. Appropriate tissue samples are available for analysis 4. Life expectancy \> 6 weeks 5. Written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Personalized medicine recommendation | 5 years | Proportion of patients for whom personalized medicine recommendation can be made using a comprehensive diagnostic platform within a clinically relevant timeframe |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor samples with actionable molecular alterations | 5 years | Proportion of tumor samples found to have actionable molecular alterations |
| Successfully conducted in vitro high throughput drug screening and in vivo drug sensitivity testing | 5 years | Proportion of tumours where in vitro high throughput drug screening and in vivo drug sensitivity testing can be successfully performed |
| Identification of potential treatment by in vitro or in vivo drug screening | 5 years | Proportion of tumors for which a potential treatment option is identified by in vitro or in vivo drug screening |
| Patients receiving the recommended personalized therapy | 5 years | Proportion of patients who subsequently receive the recommended personalized therapy |
| Barriers or reasons for patients not receiving the recommended personalized therapy | 5 years | Description of the barriers or reasons for patients not receiving the recommended personalized therapy |
| Reporting turnaround time | 5 years | Number of weeks from enrollment to issuing a report to the treating clinician |
Other
| Measure | Time frame | Description |
|---|---|---|
| Impact of personalized therapy on progression-free survival | Up to 5 years | Time interval from enrollment until disease progression or death for patients who have received personalized therapy versus those who have not |
| Impact of personalized therapy on overall survival | Up to 5 years | Time interval from enrollment until death for patients who have received personalized therapy versus those who have not |
Countries
Australia
Outcome results
None listed