Precision Medicine for Every Child With Cancer

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	0 Years - 25 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05504772
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Australian & New Zealand Children's Haematology/Oncology Group
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	David Ziegler
Principal Investigator Affiliation	SCHN
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Australia
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor, Childhood Leukemia, Refractory Cancer, Relapsed Cancer

Additional Details

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.

Arms & Interventions

Arms

: High-risk cancers

One of the following two criteria must be met: Confirmed or suspected high-risk malignancy defined as expected overall survival < 30% based on current literature for the specific cancer 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.

: Rare tumors

At least one of the following three criteria must be met: A rare tumor of uncertain prognosis due to rarity of disease A rare tumor with no established treatment strategy A cancer where routine histopathological examination has not been able to establish a diagnosis Confirmed histiocytic disorder AND molecular profiling may facilitate diagnosis and/or treatment 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

: Primary central nervous system (CNS) tumours

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

: Neuroblastoma

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

: 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)

: 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)

: Lymphomas

Patient is suspected or confirmed to have a lymphoma

: 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)

: Renal tumors

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

: Hepatic and biliary tree tumors

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

: Thyroid and endocrine tumors

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

: Other tumors

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

: Germline only

One of the following two criteria must be met: Patients whose submitted tumor sample could not yield sufficient DNA for any molecular analysis AND participants/parents have consented to return of germline findings. 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.

Interventions

Genetic: - 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.

Genetic: - RNA seq

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

Genetic: - DNA Methylation

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

Genetic: - Targeted Panel Sequencing

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

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.

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.

Other: - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.