Neuroblastoma Precision Trial

Official Title

N2015-01: Neuroblastoma Precision Trial

Summary:

This proposal sets forth the platform for a Precision Medicine clinical trial through the New Approaches to Neuroblastoma Therapy (NANT) consortium. The plan is to utilize NANT's established multi-institutional infrastructure and Translational Genomics Research Institute GEM sequencing platform for acquisition and gene panel sequencing of relapsed biological specimens in relapsed/refractory neuroblastoma (rNB) including those obtained from the bone, bone marrow or soft tissue. Our primary aim is to identify subgroups of rNB patients who have potentially targetable genetic (ALK, MAPK pathway, Metabolic-related genes) and/or immunologic (tumour-associated macrophage infiltration and/or programmed death ligand [PD-L1] expression) biomarkers in rNB. Additional potential novel biomarkers will also be evaluated and reported in this cohort of patients.

Trial Description

Primary Outcome:

• Identify genomic alterations, whether targetable alterations are present and within 4 defined NBL subgroups or outside of these 4 defined NBL subgroups. Identify presence/absence of immunologic biomarkers common to NBL.

Secondary Outcome:

• How many subjects are biopsied or provide available tumour that is found to be adequate for gene panel sequencing and produces a clinical report
• How many patients with bone marrow aspirates performed that contain < 30% tumour cells are able to be enriched and genetic alterations identified

Neuroblastoma (NB) is the most common extracranial solid tumour of childhood. High-risk NB is highly lethal and responsible for over 15% of childhood cancer related deaths. The majority of patients with metastatic NB respond to upfront cytotoxic chemotherapy, yet patients who die of recurrent disease do so from tumour acquired resistance to treatment. Thus, understanding the repertoire of tumour specific genomic alterations leading to tumour progression and therapy resistance is critical to devising novel targeted therapy options for patients with recurrent or refractory (r)NB. Limited data exists regarding the genetic and immunologic predictive biomarkers in rNB, which can be used to direct targeted therapies. Another barrier to clinical implementation of genetic testing of tumour samples from children with rNB is obtaining sufficient number of tumour cells from bone marrow (BM) specimens, the most easily accessible and common site of relapse. This proposal sets forth the platform for a Precision Medicine clinical trial through the New Approaches to Neuroblastoma Therapy (NANT) consortium. The plan is to utilize NANT's established multi-institutional infrastructure and Translational Genomics Research Institute (TGen) GEMTM sequencing platform for acquisition and gene panel sequencing of relapsed biological specimens in rNB including those obtained from the bone, bone marrow or soft tissue. Our primary aim is to identify subgroups of rNB patients who have potentially targetable genetic (ALK, MAPK pathway, Metabolic-related genes) and/or immunologic (tumour-associated macrophage infiltration and/or PD-L1 expression) biomarkers in rNB. Additional potential novel biomarkers will also be evaluated and reported in this cohort of patients. This aim has immediate impact on the lives of children with rNB as it provides a clinical report to patients and their physicians detailing observed mutations and rNB subgroups and information on clinical trials that best match them. Our second aim will assess a novel method for enriching tumour cells from bone marrow aspirates containing less than 30% tumour involvement so that next generation sequencing can be performed. Our bone marrow (BM) enrichment protocol has both methodological and patient significance; 1) BM enrichment will allow a much larger group of rNB patients access to future personalized medicine trials and 2) Successful confirmation that BM enrichment can produce quality DNA for genetic analysis serves as proof of principal that this method can be used for genetic testing of BM with evidence of metastasis in other adult or pediatric solid tumours. In summary, our proposal will define the genetic and immunologic landscape of rNB and contribute to our understanding and ability to therapeutically target the dynamic alterations in tumour biology of children with rNB.

View this trial on ClinicalTrials.gov