Precision Medicine for Every Child With Cancer (ZERO2)

Australian & New Zealand Children's Haematology/Oncology Group

Status: Enrolling

Conditions: Childhood Leukemia; Relapsed Cancer; Childhood Solid Tumor; Refractory Cancer; Childhood Cancer; Childhood Brain Tumor

Treatments: Other: Liquid Biopsy; Genetic: Patient Derived Xenograft (PDX)(in vivo); Genetic: Whole Genome Sequencing; Genetic: DNA Methylation; Genetic: RNA seq; Genetic: High Throughput Sequencing (in vitro); Genetic: Targeted Panel Sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT05504772

ZERO2

Details and patient eligibility

About

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

Full 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.

Enrollment: 3,500 estimated patients

Sex: All

Ages: Under 25 years old

Volunteers: No Healthy Volunteers

Inclusion and 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 design

3,500 participants in 13 patient groups

High-risk cancers

Description:

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.

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: High Throughput Sequencing (in vitro)

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Genetic: Patient Derived Xenograft (PDX)(in vivo)

Rare tumors

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Primary central nervous system (CNS) tumours

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Neuroblastoma

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

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

Description:

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)

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Acute lymphoblastic leukemia (ALL)

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Lymphomas

Description:

Patient is suspected or confirmed to have a lymphoma

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Sarcomas

Description:

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)

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Renal tumors

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Hepatic and biliary tree tumors

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Thyroid and endocrine tumors

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Other tumors

Description:

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

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy

Germline only

Description:

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.

Treatment:

Genetic: Targeted Panel Sequencing

Genetic: RNA seq

Genetic: DNA Methylation

Genetic: Whole Genome Sequencing

Other: Liquid Biopsy