NCT05504772

Brief Summary

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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,500

participants targeted

Target at P75+ for all trials

Timeline
51mo left

Started Dec 2022

Longer than P75 for all trials

Geographic Reach
2 countries

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress45%
Dec 2022Jul 2030

First Submitted

Initial submission to the registry

January 30, 2022

Completed
7 months until next milestone

First Posted

Study publicly available on registry

August 17, 2022

Completed
4 months until next milestone

Study Start

First participant enrolled

December 16, 2022

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2025

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2030

Expected
Last Updated

July 17, 2024

Status Verified

July 1, 2024

Enrollment Period

2.5 years

First QC Date

January 30, 2022

Last Update Submit

July 16, 2024

Conditions

Keywords

childrenprecision medicinepersonalised medicinemolecular profilingpediatricpaediatric

Outcome Measures

Primary Outcomes (2)

  • Utility of recommended personalized therapy for HR childhood cancer patients.

    Disease control rate (stable disease + partial response + complete response) in HR patients who have received recommended personalized therapy which are molecularly and/or preclinically directed

    5 years

  • Utility of recommended personalized therapy for non-HR childhood cancer patients.

    The proportion of non-HR patients for whom the disease specific, clinically relevant, virtual molecular panel provides additional or equivalent results for diagnosis and risk stratification when compared with routine diagnostic tests.

    5 years

Secondary Outcomes (6)

  • Utility of pre-defined virtual molecular panel for non-HR childhood cancer patients.

    5 years

  • Utility of comprehensive precision medicine for patients with rare tumors in childhood.

    5 years

  • Utility of Molecular Tumour Board (MTB) recommendation tier system for HR childhood cancer patients.

    5 years

  • Utility of preclinical testing in HR childhood cancer patients.

    5 years

  • Clinical utility of germline WGS in patients with childhood cancers.

    5 years

  • +1 more secondary outcomes

Study Arms (13)

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.

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingGenetic: High Throughput Sequencing (in vitro)Genetic: Patient Derived Xenograft (PDX)(in vivo)Other: Liquid Biopsy

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Primary central nervous system (CNS) tumours

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Neuroblastoma

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

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)

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

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)

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Lymphomas

Patient is suspected or confirmed to have a lymphoma

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

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)

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Renal tumors

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Hepatic and biliary tree tumors

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Thyroid and endocrine tumors

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Other tumors

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

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

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.

Genetic: Whole Genome SequencingGenetic: RNA seqGenetic: DNA MethylationGenetic: Targeted Panel SequencingOther: Liquid Biopsy

Interventions

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.

Acute lymphoblastic leukemia (ALL)Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALLGermline onlyHepatic and biliary tree tumorsHigh-risk cancersLymphomasNeuroblastomaOther tumorsPrimary central nervous system (CNS) tumoursRare tumorsRenal tumorsSarcomasThyroid and endocrine tumors
RNA seqGENETIC

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

Acute lymphoblastic leukemia (ALL)Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALLGermline onlyHepatic and biliary tree tumorsHigh-risk cancersLymphomasNeuroblastomaOther tumorsPrimary central nervous system (CNS) tumoursRare tumorsRenal tumorsSarcomasThyroid and endocrine tumors

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

Acute lymphoblastic leukemia (ALL)Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALLGermline onlyHepatic and biliary tree tumorsHigh-risk cancersLymphomasNeuroblastomaOther tumorsPrimary central nervous system (CNS) tumoursRare tumorsRenal tumorsSarcomasThyroid and endocrine tumors

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

Acute lymphoblastic leukemia (ALL)Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALLGermline onlyHepatic and biliary tree tumorsHigh-risk cancersLymphomasNeuroblastomaOther tumorsPrimary central nervous system (CNS) tumoursRare tumorsRenal tumorsSarcomasThyroid and endocrine tumors

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

High-risk cancers

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

High-risk cancers

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)Acute myeloid leukemia, myelodysplastic syndrome and other leukemias not classified as ALLGermline onlyHepatic and biliary tree tumorsHigh-risk cancersLymphomasNeuroblastomaOther tumorsPrimary central nervous system (CNS) tumoursRare tumorsRenal tumorsSarcomasThyroid and endocrine tumors

Eligibility Criteria

Age0 Years - 25 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Patients \<18 years of age with a diagnosis of tumor or cancer Patients aged 19 - 25 years with a diagnosis of a pediatric tumor or cancer

You may qualify if:

  • 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.
  • Life expectancy \>6 weeks at time of enrolment
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Women's and Children's Hospital

Adelaide, Australia

RECRUITING

Queensland Children's Hospital

Brisbane, Australia

RECRUITING

Royal Hobart Hospital

Hobart, Australia

RECRUITING

Monash Children's Hospital

Melbourne, Australia

RECRUITING

Royal Children's Hospital

Melbourne, Australia

RECRUITING

John Hunter Children's Hospital

Newcastle, Australia

RECRUITING

Perth Children's Hospital

Perth, Australia

RECRUITING

Sydney Children's Hospital, Randwick

Sydney, Australia

RECRUITING

The Children's Hospital at Westmead

Sydney, Australia

RECRUITING

Starship Children's Hospital

Auckland, Grafton, 1023, New Zealand

RECRUITING

Christchurch Hospital

Christchurch, 8011, New Zealand

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumour, blood, bone marrow, cerebrospinal fluid (CSF), urine, skin biopsy, cytogenetic culture, extracted DNA and peripheral blood stem cells.

MeSH Terms

Conditions

NeoplasmsRecurrence

Interventions

Whole Genome SequencingBase SequenceDNA MethylationHigh-Throughput Nucleotide SequencingIn Vitro TechniquesLiquid Biopsy

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNASequence AnalysisGenetic TechniquesInvestigative TechniquesMolecular StructureBiochemical PhenomenaChemical PhenomenaGenetic StructuresGenetic PhenomenaMethylationAlkylationMetabolismBiopsyCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen Handling

Study Officials

  • David Ziegler

    SCHN

    PRINCIPAL INVESTIGATOR

Central Study Contacts

National Study Coordinator

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2022

First Posted

August 17, 2022

Study Start

December 16, 2022

Primary Completion

July 1, 2025

Study Completion (Estimated)

July 1, 2030

Last Updated

July 17, 2024

Record last verified: 2024-07

Locations