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Neuroblastoma Precision Trial

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ClinicalTrials.gov Identifier: NCT02868268
Recruitment Status : Active, not recruiting
First Posted : August 16, 2016
Last Update Posted : January 20, 2021
Sponsor:
Collaborators:
Children's Hospital Los Angeles
The Evan Foundation
St. Baldrick's Foundation
Press On Fund
Rising Tide Foundation
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium

Tracking Information
First Submitted Date June 3, 2016
First Posted Date August 16, 2016
Last Update Posted Date January 20, 2021
Study Start Date August 2016
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 11, 2016)
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. [ Time Frame: 6 weeks ]
Archival or biopsied tumor specimens undergo gene panel sequencing and/or immunohistochemistry and a list of all genetic/immunologic alterations are identified. Was an actionable genetic alteration identified and were any of these alterations within 4 NBL specific subgroups (ALK, MAPK, Metabolic, Immune reactive) or outside of the 4 NBL specific subgroups.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: August 11, 2016)
  • How many subjects are biopsied or provide available tumor that is found to be adequate for gene panel sequencing and produces a clinical report [ Time Frame: 6 weeks ]
    Identify number of subjects who successfully provide tumor from either a procedure or archival sources and whether this tumor is adequate for analysis (>= 30% tumor present/specimen) as determined locally and centrally. Of these specimens that are found to be adequate and sent to the gene sequencing center, how many result in a clinical report being issued.
  • How many patients with bone marrow aspirates performed that contain < 30% tumor cells are able to be enriched and genetic alterations identified [ Time Frame: 1 year ]
    Identify number of subjects who successfully provide tumor from either a bone marrow aspiration or archival sources and < 30% tumor present. Was tumor enrichment attempted and # of patients where enrichment was attempted and successful to allow gene sequencing and identification of genetic/immunologic alterations. Was an actionable genetic alteration identified and were any of these alterations within 4 NBL specific subgroups (ALK, MAPK, Metabolic, Immune reactive) or outside of the 4 NBL specific subgroups.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Neuroblastoma Precision Trial
Official Title N2015-01: Neuroblastoma Precision Trial
Brief 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 (tumor-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.
Detailed Description Neuroblastoma (NB) is the most common extracranial solid tumor 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 tumor acquired resistance to treatment. Thus, understanding the repertoire of tumor specific genomic alterations leading to tumor 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 tumor samples from children with rNB is obtaining sufficient number of tumor 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 (tumor-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 tumor cells from bone marrow aspirates containing less than 30% tumor 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 tumors. 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 tumor biology of children with rNB.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood obtained (any time prior to and up to the day of biopsy) Biopsy of soft tissue, bone, bone marrow Specimens tumor content for genetic +/- IHC analysis.
Sampling Method Non-Probability Sample
Study Population High risk neuroblastoma
Condition Neuroblastoma
Intervention Other: Gene panel sequencing of tumor specimens
Archival or biopsied tumor specimens will undergo gene panel sequencing to identify subgroups with targetable genetic (ALK, MAPK pathway, Metabolic-related genes) and/or immunologic (tumor associated macrophage infiltration, PD-L1 expression) biomarkers in neuroblastoma. A clinical report will be provided to subjects/subject physician detailing observed mutations and identified NBL subgroups and information on clinical trials that best match them. Subjects will be followed and data collected on treatments administered for one year after receipt of clinical report.
Study Groups/Cohorts Relapsed/Refractory Neuroblastoma Pts
History of high risk neuroblastoma (NBL) according to Childrens Oncology Group (COG) risk classification with relapsed/progressive, refractory or persistent neuroblastoma. Archival or biopsied tumor specimens are provided for gene panel sequencing to subjects with potentially targetable genetic and/or immunologic biomarkers. A clinical report will be provided to subjects/subject physician detailing observed mutations and identified NBL subgroups and information on clinical trials that best match them. Subjects will be followed and data collected on treatments administered for one year after receiving this clinical report.
Intervention: Other: Gene panel sequencing of tumor specimens
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: January 15, 2021)
93
Original Estimated Enrollment
 (submitted: August 11, 2016)
90
Estimated Study Completion Date July 2022
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients must be ≥ 1 year and ≤ 30 years of age at study registration
  • Patients must have had a diagnosis of neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
  • Patients must have a history of high-risk neuroblastoma according to
  • COG risk classification at the time of study registration. Patients must have at least one of the following: Recurrent/progressive disease, Refractory disease, Persistent disease
  • Patient must be willing to undergo a clinically indicated biopsy and meet at least one of the following requirements: Bone biopsy, Soft tissue biopsy, Bone marrow biopsy and aspirate
  • Patients must not be receiving any other anti-cancer agents or radiotherapy during the interval

Exclusion Criteria:

  • Patients with disease of any major organ system that would compromise their ability to withstand biopsy procedures of soft tissue, bone and/or bone marrow.
  • Patients who enroll and successfully receive a NANT Precision Report may not re-enroll at a future time.
  • Patient declines participation in NANT 2004-05, the NANT Biology Study.
Sex/Gender
Sexes Eligible for Study: All
Ages 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries Canada
 
Administrative Information
NCT Number NCT02868268
Other Study ID Numbers N2015-01
N2015-01 ( Other Identifier: NANT Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: Individual participant data will be shared with the treating investigator and the study participant.
Responsible Party New Approaches to Neuroblastoma Therapy Consortium
Study Sponsor New Approaches to Neuroblastoma Therapy Consortium
Collaborators
  • Children's Hospital Los Angeles
  • The Evan Foundation
  • St. Baldrick's Foundation
  • Press On Fund
  • Rising Tide Foundation
Investigators
Study Chair: Shahab Asgharzadeh, MD Children's Hospital Los Angeles
PRS Account New Approaches to Neuroblastoma Therapy Consortium
Verification Date January 2021