PRISM: PRecISion Medicine for Children With Cancer

Sponsor

Sydney Children's Hospitals Network (Other)

Overall Status

Recruiting

CT.gov ID

NCT03336931

Collaborator

Children's Cancer Institute Australia (Other), Australian & New Zealand Children's Haematology/Oncology Group (Other), Garvan Institute of Medical Research (Other), German Cancer Research Center (Other)

550

Enrollment

Locations

143.9

Anticipated Duration (Months)

68.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Cancer Childhood Solid Tumor Childhood Brain Tumor Childhood Leukemia Refractory Cancer Relapsed Cancer	Diagnostic Test: Molecular profiling and drug testing

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

550 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 5, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
High-risk childhood cancers Expected survival < 30%	Diagnostic Test: Molecular profiling and drug testing 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

Arm

Intervention/Treatment

High-risk childhood cancers

Expected survival < 30%

Diagnostic Test: Molecular profiling and drug testing

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
Reporting turnaround time [5 years]
Number of weeks from enrollment to issuing a report to the treating clinician
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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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, Randwick	Sydney	New South Wales	Australia	2031
3	The Children's Hospital at Westmead	Sydney	New South Wales	Australia	2145
4	Queensland Children's Hospital	Brisbane	Queensland	Australia	4101
5	Women's and Children's Hospital	Adelaide	South Australia	Australia	5006
6	Royal Children's Hospital	Melbourne	Victoria	Australia	3052
7	Monash Children's Hospital	Melbourne	Victoria	Australia	3168
8	Perth Children's Hospital	Perth	Western Australia	Australia	6008