Precision Medicine for Every Child With Cancer

NCT ID: NCT05504772

Last Updated: 2024-07-17

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

RECRUITING

Total Enrollment

3500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-12-16

Study Completion Date

2030-07-31

Brief Summary

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To improve outcomes for childhood cancer patients through the implementation of precision medicine.

Detailed Description

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Through the pilot TARGET and national PRISM trials the feasibility and benefits of using comprehensive molecular profiling and preclinical drug testing in real time for high-risk (HR) patients has been demonstrated. However, the role of precision medicine, especially in facilitating diagnosis and risk stratification in non-HR childhood cancers has not been studied. Integrative tumor-germline whole genome sequencing (WGS) analysis has the potential to advance our understanding of cancer predisposition. In this study, the ZERO platform will be extended to all children with cancer in Australia and New Zealand, evaluating the benefits of precision medicine in different childhood cancer types and risk groups.

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 cancers

One of the following two criteria must be met:

1. Confirmed or suspected high-risk malignancy defined as expected overall survival \< 30% based on current literature for the specific cancer
2. Cancers for which standard therapy would result in unacceptable and severe morbidity (e.g., infantile fibrosarcoma where definitive surgery would require amputation of limb) Note: This does not include HR neuroblastoma at diagnosis as this group of patients have an overall survival ≥30% and belongs to Cohort 4A.

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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)

Intervention Type GENETIC

High 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)

Intervention Type GENETIC

In 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

Intervention Type OTHER

Liquid 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.

Rare tumors

At least one of the following three criteria must be met:

1. A rare tumor of uncertain prognosis due to rarity of disease
2. A rare tumor with no established treatment strategy
3. A cancer where routine histopathological examination has not been able to establish a diagnosis
4. Confirmed histiocytic disorder AND molecular profiling may facilitate diagnosis and/or treatment
5. Confirmed proliferative vascular or lymphatic malformation AND has failed conventional treatment, e.g., surgery or embolization, OR no appropriate treatment is available AND the disease is organ, limb or life threatening, or debilitating

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Primary central nervous system (CNS) tumours

Patient is suspected or confirmed to have a primary CNS tumor, including low and high-grade tumors

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Neuroblastoma

Patient is suspected or confirmed to have neuroblastoma 4A: HR neuroblastoma at diagnosis 4B: Non-HR neuroblastoma

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALL

Patient is confirmed by flow cytometry to have acute myeloid leukemia (AML) or other leukemias (Note: Verbal confirmation of flow cytometry result is adequate for enrolment)

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Acute lymphoblastic leukemia (ALL)

Patient is confirmed to have acute lymphoblastic leukemia by flow cytometry (Note: Verbal confirmation of flow cytometry result is adequate for enrolment)

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Lymphomas

Patient is suspected or confirmed to have a lymphoma

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Sarcomas

Patient is suspected or confirmed to have a sarcoma Includes gastrointestinal stromal tumour (GIST), malignant peripheral nerve sheath tumour (MPNST), desmoplastic small round cell tumour (DSRCT)

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Renal tumors

Patient is suspected or confirmed to have a renal tumor Includes clear cell sarcoma of kidney

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Hepatic and biliary tree tumors

Patient is suspected or confirmed to have a liver or biliary tree tumor

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Thyroid and endocrine tumors

Patient is suspected or confirmed to have a thyroid or endocrine cancer

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Other tumors

Patient is suspected or confirmed to have a tumor which does not fit into any of the above

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Germline only

One of the following two criteria must be met:

1. Patients whose submitted tumor sample could not yield sufficient DNA for any molecular analysis AND participants/parents have consented to return of germline findings.
2. Patients who do not have appropriate tumor sample to be submitted for molecular profiling may be considered for germline only analysis. Obtaining tumor samples wherever possible will be encouraged.

Whole Genome Sequencing

Intervention Type GENETIC

Each 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

Intervention Type GENETIC

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

DNA Methylation

Intervention Type GENETIC

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Targeted Panel Sequencing

Intervention Type GENETIC

Targeted 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

Liquid Biopsy

Intervention Type OTHER

Liquid 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.

Interventions

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Whole Genome Sequencing

Each 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.

Intervention Type GENETIC

RNA seq

Results will be used for bioinformatics analysis for fusion transcripts and gene expression.

Intervention Type GENETIC

DNA Methylation

Genome-wide assessment of DNA methylation will be conducted on all samples where possible.

Intervention Type GENETIC

Targeted Panel Sequencing

Targeted 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

Intervention Type GENETIC

High Throughput Sequencing (in vitro)

High throughput drug screening will be attempted for tumors from Cohort 1 (high-risk cancers with survival \<30%) and selected tumor types.

Intervention Type GENETIC

Patient Derived Xenograft (PDX)(in vivo)

In vivo drug testing in patient derived xenograft (PDX) will be attempted for tumors from Cohort 1 (high-risk cancers) and selected tumor types.

Intervention Type GENETIC

Liquid Biopsy

Liquid 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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. Life expectancy \>6 weeks at time of enrolment
3. 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.
Minimum Eligible Age

0 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Cancer Institute (CCI)

UNKNOWN

Sponsor Role collaborator

Minderoo Foundation

UNKNOWN

Sponsor Role collaborator

Medical Research Future Fund

OTHER

Sponsor Role collaborator

Australian & New Zealand Children's Haematology/Oncology Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Ziegler

Role: PRINCIPAL_INVESTIGATOR

SCHN

Locations

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Women's and Children's Hospital

Adelaide, , Australia

Site Status RECRUITING

Queensland Children's Hospital

Brisbane, , Australia

Site Status RECRUITING

Royal Hobart Hospital

Hobart, , Australia

Site Status RECRUITING

Monash Children's Hospital

Melbourne, , Australia

Site Status RECRUITING

Royal Children's Hospital

Melbourne, , Australia

Site Status RECRUITING

John Hunter Children's Hospital

Newcastle, , Australia

Site Status RECRUITING

Perth Children's Hospital

Perth, , Australia

Site Status RECRUITING

Sydney Children's Hospital, Randwick

Sydney, , Australia

Site Status RECRUITING

The Children's Hospital at Westmead

Sydney, , Australia

Site Status RECRUITING

Starship Children's Hospital

Auckland, Grafton, New Zealand

Site Status RECRUITING

Christchurch Hospital

Christchurch, , New Zealand

Site Status NOT_YET_RECRUITING

Countries

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Australia New Zealand

Central Contacts

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National Study Coordinator

Role: CONTACT

+61 2 9382 3102

Facility Contacts

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Suzanne Milne

Role: primary

Natasha Brown

Role: primary

David Nolan

Role: primary

Amanda St John

Role: primary

Kahlia Fox

Role: primary

Rebecca Jensen

Role: primary

Jennifer McConnell

Role: primary

Sandra Montez

Role: primary

Jun Christian

Role: primary

Sarah Hunter

Role: primary

Kirstie Copeland

Role: primary

Other Identifiers

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ZERO2

Identifier Type: -

Identifier Source: org_study_id

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