Testing Cerebrospinal Fluid for Cell-free Tumor DNA in Children, Adolescents, and Young Adults With Brain Tumors

NCT05934630 | Terminated DMC

• 3 other identifiers: PBTC-N14UM1CA081457NCI-2023-02321
• Study Type: observational
• Target: 57
• Locations: 2 countries
• Sites: 10

Brief Summary

Recent advances in technology have allowed for the detection of cell-free DNA (cfDNA). cfDNA is tumor DNA that can be found in the fluid that surrounds the brain and spinal cord (called cerebrospinal fluid or CSF) and in the blood of patients with brain tumors. The detection of cfDNA in blood and CSF is known as a "liquid biopsy" and is non-invasive, meaning it does not require a surgery or biopsy of tumor tissue. Multiple studies in other cancer types have shown that cfDNA can be used for diagnosis, to monitor disease response to treatment, and to understand the genetic changes that occur in brain tumors over time. Study doctors hope that by studying these tests in pediatric brain tumor patients, they will be able to use liquid biopsy in place of tests that have more risks for patients, like surgery. There is no treatment provided on this study. Patients who have CSF samples taken as part of regular care will be asked to provide extra samples for this study. The study doctor will collect a minimum of one extra tube of CSF (about 1 teaspoon or 5 mL) for this study. If the patients doctor thinks it is safe, up to 2 tubes of CSF (about 4 teaspoons or up to 20 mL) may be collected. CSF will be collected through the indwelling catheter device or through a needle inserted into the lower part of the patient's spine (known as a spinal tap or lumbar puncture). A required blood sample (about ½ a teaspoon or 2 3 mL) will be collected once at the start of the study. This sample will be used to help determine changes found in the CSF. Blood will be collected from the patient's central line or arm as a part of regular care. An optional tumor tissue if obtained within 8 weeks of CSF collection will be collected if available. Similarities between changes in the DNA of the tissue that has caused the tumor to form and grow with the cfDNA from CSF will be compared. This will help understand if CSF can be used instead of tumor tissue for diagnosis. Up to 300 people will take part in this study. This study will use genetic tests that may identify changes in the genes in the CSF. The report of the somatic mutations (the mutations that are found in the tumor only) will become part of the medical record. The results of the cfDNA sequencing will be shared with the patient. The study doctor will discuss what the results mean for the patient and patient's diagnosis and treatment. Looking for inheritable mutations in normal cells (blood) is not the purpose of this study. Genetic tests of normal blood can reveal information about the patient and also about the their relatives. The doctor will discuss what the tests results may mean for the patient and the their family. Patient may be monitored on this study for up to 5 years.

Conditions

Glioblastoma Multiforme; High-grade Astrocytoma NOS; Fibrillary Astrocytoma; Low-Grade Astrocytoma, Nos; Pilocytic Astrocytoma; Choroid Plexus Carcinoma; CNS Primary Tumor, Nos; Atypical Teratoid/Rhabdoid Tumor; Medulloblastoma; Supratentorial Primitive Neuroectodermal Tumor; Ependymoma, NOS; Anaplastic Oligodendroglioma; Oligodendroglioma, Nos; CNS Germ Cell Tumor; Pineoblastoma; Anaplastic Astrocytoma; Diffuse Brainstem Glioma; Diffuse Leptomeningeal Glioneuronal Tumor

Keywords

Liquid biopsy; CSF; Cerebrospinal fluid; cfDNA; ctDNA; Pediatric central nervous system tumors; Brain tumor

Outcome Measures

Primary Outcomes (1)

• Concordance of mutations across the tumor tissue vs. CSF

  Within specific histologies with paired samples, estimate the concordance of mutation detected in the tumor tissue vs. cerebrospinal fluid cell free DNA (CSF cfDNA) across samples collected within 8 weeks of each other.

  3 months

Secondary Outcomes (2)

• Estimate the frequency of detection of CSF cfDNA across different types of pediatric CNS tumors in association with various disease states.

  3 months

• Track and estimate the correlation between the levels of CSF cfDNA and disease response as determined by clinical and imaging criteria across different disease types.

  3 months

Study Arms (6)

Stratum 1: Medulloblastoma

Participants in Arm 1 must have diagnosis of Medulloblastoma. All children and adolescent/young adult (AYA) patients \<= 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults.

Stratum 2: High-grade Glioma (IDH-wildtype) or Diffuse Intrinsic Pontine Glioma

Participants in Arm 2 must have diagnosis of High-grade Glioma (IDH-wildtype) or Diffuse Intrinsic Pontine Glioma (DIPG). All children and adolescent/young adult (AYA) patients \<= 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults. DIPG patients must meet clinical and imaging requirements for DIPG diagnosis. Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of 2/5 or more of the pons, are eligible without histologic confirmation. Patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible for Stratum 2 if the tumors have been biopsied and are proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma or fibrillary astrocytoma.

Stratum 3: Low-grade Glioma IDH-wildtype with multifocal/disseminated and/or leptomeningeal disease

Participants in Arm 3 must have diagnosis of Low-grade Glioma (IDH-wildtype) with multifocal/disseminated and/or leptomeningeal disease. All children and adolescent/young adult (AYA) patients =\< 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults.

Stratum 4: Diffuse Leptomeningeal Glioneuronal Tumor

Participants in Arm 4 must have diagnosis of Diffuse Leptomeningeal Glioneuronal Tumor. All children and adolescent/young adult (AYA) patients =\< 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults.

Stratum 5: Pineoblastoma

Participants in Arm 5 must have diagnosis of Pineoblastoma. All children and adolescent/young adult (AYA) patients =\< 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults.

Stratum 6: All other eligible primary brain tumor types

Participants in Arm 6 must have diagnosis of all other eligible primary brain tumor types. All children and adolescent/young adult (AYA) patients =\< 21 years of age are eligible. AYA patients \< 40 are eligible with a primary brain tumor entity more common in children than adults.

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients will enroll from and be seen at Pediatric Brain Tumor Consortium sites and will meet the eligibility criteria in order to participate.

You may qualify if:

• All patients must have a known or suspected diagnosis (based on pathology or imaging) of a primary brain tumor. All children and adolescent/young adult (AYA) patients =\&lt; 21 years of age are eligible.
• AYA patients \&lt; 40 are eligible with a primary brain tumor entity more common in children than adults. This includes:
• medulloblastoma
• non-medulloblastoma embryonal brain tumors
• atypical teratoid rhabdoid tumors (ATRT)
• ependymoma
• CNS germ cell tumors
• Diffuse midline glioma, H3K27M-altered
• Diffuse hemispheric glioma, H3 G34-mutant
• pineoblastoma
• diffuse leptomeningeal glioneuronal tumor
• diffuse brainstem glioma
• pilocytic astrocytoma
• choroid plexus carcinoma
• ELIGIBLE PATIENTS WILL BE STRATIFIED BY DIAGNOSIS AS FOLLOWS:

You may not qualify if:

• DIAGNOSIS: Given the extremely low rate of CSF cfDNA positivity in patients with localized, non-disseminated low-grade glioma, those patients will be excluded from participation.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• American Lebanese Syrian Associated Charities: collaborator

Study Sites (10)

Children's Hospital of Los Angeles

Los Angeles, California, 90026, United States

Location

Lucille Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Choroid Plexus Carcinoma; Central Nervous System Neoplasms; Rhabdoid Tumor; Medulloblastoma; Ependymoma; Oligodendroglioma; Pinealoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Neoplasms, Complex and Mixed; Neuroectodermal Tumors, Primitive; Brain Diseases; Central Nervous System Diseases

Study Officials

• Alexandra Miller, MD, PhD

  NYU Langone Health

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start: July 12, 2023
• Primary Completion: April 17, 2026
• Study Completion: April 17, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 6 months after publication and end timeframe may be up to 10 years.

Locations

US (9); CA (1)