PRecISion Medicine for Children With Cancer

NCT ID: NCT03336931

Last Updated: 2024-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

550 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-05

Study Completion Date

2032-12-31

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.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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High-risk childhood cancers

Expected survival \< 30%

Molecular profiling and drug testing

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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Molecular 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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Cancer Institute Australia

UNKNOWN

Sponsor Role collaborator

Australian & New Zealand Children's Haematology/Oncology Group

OTHER

Sponsor Role collaborator

Garvan Institute of Medical Research

OTHER

Sponsor Role collaborator

German Cancer Research Center

OTHER

Sponsor Role collaborator

Sydney Children's Hospitals Network

OTHER

Sponsor Role lead

Responsible Party

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Dr David Ziegler

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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A/Prof David Ziegler, MBBS

Role: PRINCIPAL_INVESTIGATOR

Sydney Children's Hospitals Network

Locations

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John Hunter Children's Hospital

Newcastle, New South Wales, Australia

Site Status

Sydney Children's Hospital, Randwick

Sydney, New South Wales, Australia

Site Status

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

Site Status

Queensland Children's Hospital

Brisbane, Queensland, Australia

Site Status

Women's and Children's Hospital

Adelaide, South Australia, Australia

Site Status

Royal Children's Hospital

Melbourne, Victoria, Australia

Site Status

Monash Children's Hospital

Melbourne, Victoria, Australia

Site Status

Perth Children's Hospital

Perth, Western Australia, Australia

Site Status

Countries

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Australia

References

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Robertson EG, Hetherington K, Hunter JD, McGillycuddy M, Venkatesha V, Lau LMS, Khuong-Quang DA, Ziegler DS, Wakefield CE. Whatever It Takes: Parents' Perspectives of Patient-Derived Xenograft Mouse Models for Poor Prognosis Childhood Cancer. JCO Precis Oncol. 2025 Apr;9:e2400840. doi: 10.1200/PO-24-00840. Epub 2025 Apr 10.

Reference Type DERIVED
PMID: 40209140 (View on PubMed)

Lau LMS, Khuong-Quang DA, Mayoh C, Wong M, Barahona P, Ajuyah P, Senapati A, Nagabushan S, Sherstyuk A, Altekoester AK, Fuentes-Bolanos NA, Yeung V, Sullivan A, Omer N, Diamond Y, Jessop S, Battaglia L, Zhukova N, Cui L, Lin A, Gifford AJ, Fleuren EDG, Dalla-Pozza L, Moore AS, Khaw SL, Eisenstat DD, Gottardo NG, Wood PJ, Tapp H, Alvaro F, McCowage G, Nicholls W, Hansford JR, Manoharan N, Kotecha RS, Mateos MK, Lock RB, Tyrrell V, Haber M, Trahair TN, Cowley MJ, Ekert PG, Marshall GM, Ziegler DS. Precision-guided treatment in high-risk pediatric cancers. Nat Med. 2024 Jul;30(7):1913-1922. doi: 10.1038/s41591-024-03044-0. Epub 2024 Jun 6.

Reference Type DERIVED
PMID: 38844796 (View on PubMed)

Ajuyah P, Mayoh C, Lau LMS, Barahona P, Wong M, Chambers H, Valdes-Mora F, Senapati A, Gifford AJ, D'Arcy C, Hansford JR, Manoharan N, Nicholls W, Williams MM, Wood PJ, Cowley MJ, Tyrrell V, Haber M, Ekert PG, Ziegler DS, Khuong-Quang DA. Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes. Sci Rep. 2023 Mar 7;13(1):3775. doi: 10.1038/s41598-023-30395-4.

Reference Type DERIVED
PMID: 36882456 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32580982 (View on PubMed)

Other Identifiers

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PRISM

Identifier Type: -

Identifier Source: org_study_id

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