Clinical trial NCT05238909: Developing Biomarkers of Plexiform Tumor Burden in Patients With Neurofibromatosis-Type 1
Official title: Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neurofibromatosis 1
NF1
Neurofibromatosis Type 1
Keywords: NF1
Plexiform neurofibromas
neurofibromatosis type 1
neurofibromas
Lead sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Children's Hospital Medical Center, Cincinnati
First posted: 2022-02-14
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from the NF1 Clinical Program at Lurie Children's Hospital of Chicago

Brief summary: The purpose of this study is to identify tumor biomarkers in individuals with Neurofibromatosis type 1 (NF1). Biomarkers are signals that the investigator can measure that tell us about a process such as progress of a disease or treatment. Individuals with this diagnosis are at an elevated risk of developing a type of tumor called a plexiform neurofibroma. Currently, detecting the risk factors of these tumors in children is difficult and requires whole body imaging. The NF1 team at Lurie Children's established a way of using blood plasma in mice with neurofibromatosis type 1 to identify biomarkers that might signal the presence of tumors in people with NF1.

This study is an effort to create biomarker profiles of patients with NF1 with known tumors. The study team will utilize whole-body MRI and mass spectrometry (a method for identifying unknown compounds and the properties of molecules). The ultimate goal of this study is to better understand the tumor biomarkers in patients with NF1.

Detailed description: Neurofibromatosis type 1 (NF1) is a common inherited human disorder, with a frequency of approximately 1:2500 worldwide. A hallmark of NF1 is development of plexiform neurofibromas (PNFs) in 30 to 50% of NF1 patients. Currently, there are no biomarkers of tumor burden and whole-body magnetic resonance imaging (MRI) is expensive and limited to few centers. The investigator established an unbiased pipeline to identify candidate biomarker signals of tumor burden using plasma from neurofibroma-bearing DhhCre;Nf1fl/fl mice using untargeted metabolomics. Our preliminary data show that glucosylceramide (GC) is the most significantly deregulated compound in plasma from neurofibroma-bearing DhhCre;Nf1fl/fl mice. The investigator developed a novel targeted mass spectrometry method to accurately quantify multiple elevated GC and lactosylceramide (LC) species. In this proposal, the investigator will combine the clinical infrastructure of the NF1 comprehensive program and advance imaging at Ann \& Robert H. Lurie Children's Hospital of Chicago with the mass spectrometry capabilities at Cincinnati Children's Hospital Medical Center.

Taking advantage of our large, well-characterized, Lurie Children's NF1 population, the investigator propose to perform analytical validation studies of candidate GC/LC biomarker signature of tumor burden in plasma from NF1 patients with defined numbers of PNF (tumor burden) by whole body MRI. The potential outcomes of our study are identification of candidate biomarker of tumor burden that contribute to patient risk stratification, and analytical validation of GC/LC biomarker signature (context of use). Collectively, this work represents a synergistic approach for discovery and validation of biomarkers of tumor burden in NF1.

Eligibility criteria: Inclusion Criteria:

1. Individuals with known diagnosis of neurofibromatosis type 1 (NF1)

Exclusion Criteria:

1. Patient does not meet NF1 diagnostic criteria
2. Mosaic NF1 individuals
3. Pregnant at Screening
4. Patients who do not have the ability/capacity to undergo the informed consent process OR whose parent/legal guardian is unable to undergo the informed consent process.

Primary outcomes:
measure: Determine if glucosylceramide (GC) and lactosylceramide (LC) species levels correlate with tumor burden in patients with NF1
timeFrame: 1 year
measure: Test if tumor burden correlates with GC and LC signature in individuals with NF1 who are undergoing clinical treatment with MEK inhibitors
timeFrame: 1 year
measure: Assemble a longitudinal cohort of individuals with NF1 with plexiform neurofibromas (n=100) for deep phenotyping and tumor burden response to MEK inhibitors
timeFrame: 1 year
measure: Determine if glucosylceramide (GC) and lactosylceramide (LC) signature correlates with plexiform neurofibroma burden change in longitudinal cohort of 100 individuals with PNFs
timeFrame: 1 year
measure: Tumor volumetric analysis will be performed to correlate with GC/LC monitoring biomarker signature
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
Study officials:
affiliation: Ann & Robert H Lurie Children's Hospital of Chicago
name: Carlos Prada, MD
role: PRINCIPAL_INVESTIGATOR
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