PRecISion Medicine for Children With Cancer (PRISM)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Childhood Cancer; Relapsed Cancer; Refractory Cancer; Childhood Leukemia; Childhood Solid Tumor; Childhood Brain Tumor
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 550

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Children's Hospital
    • Sydney, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
    • Sydney, New South Wales, Australia, 2031
      • Sydney Children's Hospital, Randwick
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital
    • Melbourne, Victoria, Australia, 3168
      • Monash Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • Perth Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Paediatric patients who are being treated for high-risk cancer in Australia

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of personalized therapy on progression-free survival	Time interval from enrollment until disease progression or death for patients who have received personalized therapy versus those who have not	Up to 5 years
Impact of personalized therapy on overall survival	Time interval from enrollment until death for patients who have received personalized therapy versus those who have not	Up to 5 years

Collaborators and Investigators

• Sponsor: Sydney Children's Hospitals Network
• Collaborators: German Cancer Research Center; Australian & New Zealand Children's Haematology/Oncology Group; Garvan Institute of Medical Research; Children's Cancer Institute Australia
• Investigators: Principal Investigator: A/Prof David Ziegler, MBBS, Sydney Children's Hospitals Network

Publications and helpful links

General Publications

• Rapport F, Smith J, O'Brien TA, Tyrrell VJ, Mould EV, Long JC, Gul H, Braithwaite J. Development of an implementation and evaluation strategy for the Australian 'Zero Childhood Cancer' (Zero) Program: a study protocol. BMJ Open. 2020 Jun 23;10(6):e034522. doi: 10.1136/bmjopen-2019-034522.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2017
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: October 22, 2017
• First Submitted That Met QC Criteria: November 5, 2017
• First Posted (Actual): November 8, 2017

Study Record Updates

• Last Update Posted (Estimated): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: children; refractory; sequencing; recurrent; paediatric; precision medicine; molecular profiling; personalised medicine; high-risk cancer; patient derived xenograft
• Other Study ID Numbers: PRISM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No