Childhood CancerZERO2NCT05504772
Precision Medicine for Every Child With Cancer
An observational study of Childhood Cancer and Childhood Solid Tumor, run by Australian & New Zealand Children's Haematology/Oncology Group at 11 sites in 2 countries.
Trial summary
To improve outcomes for childhood cancer patients through the implementation of precision medicine. Read more about this study
- Who is it for?
- Ages 0 to 25 years
- Conditions the study is for
- Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor
- What is being tested?
- Whole Genome Sequencing, RNA seq and DNA Methylation
- How many people
- 3,500 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 16 Dec 2022to Jul 2030
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
11 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 2 countries
Australia9 sites, 9 recruiting
- Recruiting
Women's and Children's Hospital
Adelaide
Suzanne Milne, suzanne.milne@sa.gov.au
- Recruiting
Queensland Children's Hospital
Brisbane
Natasha Brown, natasha.brown@health.qld.gov.au
- Recruiting
Royal Hobart Hospital
Hobart
David Nolan, david.nolan@ths.tas.gov.au
- Recruiting
Monash Children's Hospital
Melbourne
Amanda St John, Amanda.StJohn@monashhealth.org
- Recruiting
Royal Children's Hospital
Melbourne
Kahlia Fox, clinicaltrialsmanager@rch.org.au
- Recruiting
John Hunter Children's Hospital
Newcastle
Rebecca Jensen, Rebecca.Jensen@health.nsw.gov.au
- Recruiting
Perth Children's Hospital
Perth
Jennifer McConnell, jennifer.mcconnell@health.wa.gov.au
- Recruiting
Sydney Children's Hospital, Randwick
Sydney
Sandra Montez, Sandra.Montez@health.nsw.gov.au
- Recruiting
The Children's Hospital at Westmead
Sydney
Jun Christian, jun.christian@health.nsw.gov.au
New Zealand2 sites, 2 recruiting
- Recruiting
Starship Children's Hospital
Auckland, Grafton, 1023
Sarah Hunter, SHunter@adhb.govt.nz
- Not yet recruiting
Christchurch Hospital
Christchurch, 8011
Kirstie Copeland, Kirstie.copeland@cdhb.health.nz
About this study
To improve outcomes for childhood cancer patients through the implementation of precision medicine.
Read the detailed description
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
- Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor, Childhood Leukemia, Refractory Cancer, Relapsed Cancer
- Being tested
- Whole Genome Sequencing, RNA seq, DNA Methylation, Targeted Panel Sequencing, High Throughput Sequencing (in vitro)
- Keywords
- children, precision medicine, personalised medicine, molecular profiling, pediatric, paediatric
- Medical subject headings
- Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole Genome SequencingGenetic
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 seqGenetic
Results will be used for bioinformatics analysis for fusion transcripts and gene expression.
DNA MethylationGenetic
Genome-wide assessment of DNA methylation will be conducted on all samples where possible.
Targeted Panel SequencingGenetic
Targeted panel sequencing may be performed:
- 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
- When mosaicism is suspected
- When indicated for a disease type
High Throughput Sequencing (in vitro)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)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 BiopsyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Genetic: 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 Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: 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 Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Neuroblastoma | Patient is suspected or confirmed to have neuroblastoma 4A: HR neuroblastoma at diagnosis 4B: Non-HR neuroblastoma Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: 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) Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: 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) Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Lymphomas | Patient is suspected or confirmed to have a lymphoma Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: 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) Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Renal tumors | Patient is suspected or confirmed to have a renal tumor Includes clear cell sarcoma of kidney Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Hepatic and biliary tree tumors | Patient is suspected or confirmed to have a liver or biliary tree tumor Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Thyroid and endocrine tumors | Patient is suspected or confirmed to have a thyroid or endocrine cancer Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy | |
| Other tumors | Patient is suspected or confirmed to have a tumor which does not fit into any of the above Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: 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. Receives: Genetic: Whole Genome Sequencing; Genetic: RNA seq; Genetic: DNA Methylation; Genetic: Targeted Panel Sequencing; Other: Liquid Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 5 years
Secondary outcomes (6)
Utility of pre-defined virtual molecular panel for non-HR childhood cancer patients.
The proportion of non-HR patients for whom a pre-defined virtual molecular panel; leads to a streamline molecular report issued within 4 weeks from receipt of samples, changes or refines the initial histopathological diagnosis, changes or refines risk stratification at diagnosis, changes or refines treatment at diagnosis and/or facilitates enrolment in clinical trials requiring prior molecular studies.
Measured: 5 years
Utility of comprehensive precision medicine for patients with rare tumors in childhood.
Proportion of rare cancer cohort patients for which comprehensive precision medicine improves diagnosis, identifies at least one therapeutic target or facilitates improvement in therapy within a clinically relevant timeframe.
Measured: 5 years
Utility of Molecular Tumour Board (MTB) recommendation tier system for HR childhood cancer patients.
Evaluation of the correlation of MTB recommendation tier to treatment outcome, clinician rated value of MTB recommendation tier in facilitating therapeutic decision and drug access and proportion of HR patients for which the MTB recommendation improves diagnosis, risk stratification or facilitates improvement in therapy within a clinically relevant timeframe.
Measured: 5 years
Utility of preclinical testing in HR childhood cancer patients.
Evaluation of proportion of tumors where in vitro sensitivity testing can be successfully performed compared with PRISM trial, turnaround time for preclinical in vitro and in vivo drug testing, proportion of tumors where in vitro drug sensitivity identifies additional molecular drivers and proportion of patients for whom preclinical testing:
- Facilitates therapeutic decision ii. Identifies additional therapeutic options in patients for whom genomic profiling did not identify molecular targets iii. Predicts clinical outcome
Measured: 5 years
Clinical utility of germline WGS in patients with childhood cancers.
Evaluation of;
- Proportion of HR and non-HR patients with a reportable germline finding (i. For whom the result was not previously known ii. For whom the results would have been missed using current clinical testing criteria)
- Proportion of patients for whom medical management for the current cancer and future cancer risk has been altered based on the germline findings
Measured: 5 years
Treatment outcome in HR childhood cancer patients who have received recommended personalised therapy which are molecularly and/or preclinically directed.
Evaluation of;
- Objective response in patients who have received single agent versus combination personalized therapy
- Disease control (stable disease + partial response + complete response) in patients who have received a single agent versus combination personalized therapy
- Progression-free interval (PFI) ratio: PFI personalized therapy : PFI conventional therapy
- Difference in outcome between patients have received recommended personalised therapy and those who did not (i. Proportion of patients without progression or death at 6 and 12 months between the two groups ii. Difference in progression-free and overall survival between the two groups)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2022
- Study start16 Dec 2022
- Primary completionJul 2025 (estimated)
- Study completionJul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Australian & New Zealand Children's Haematology/Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Cancer Institute (CCI), Minderoo Foundation, Medical Research Future Fund
- Responsible party
- Sponsor
- Investigators
- David Ziegler, Principal investigator, SCHN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05504772
- Sponsor's protocol ID
- ZERO2
- Acronym
- ZERO2
- Status last verified
- Jul 2024
- First submitted
- 30 Jan 2022
- Last updated
- 17 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No