Neurofibromatosis 1NCT05238909
Developing Biomarkers of Plexiform Tumor Burden in Patients With Neurofibromatosis-Type 1
An observational study of Neurofibromatosis 1 and NF1, run by Ann & Robert H Lurie Children's Hospital of Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neurofibromatosis 1, NF1, Neurofibromatosis Type 1
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2022to 30 Jun 2027
- How long will I take part?
- 1 Year
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients from the NF1 Clinical Program at Lurie Children's Hospital of Chicago
Who may be able to join
- 1. Individuals with known diagnosis of neurofibromatosis type 1 (NF1)
Who cannot join
- Patient does not meet NF1 diagnostic criteria
- Mosaic NF1 individuals
- Pregnant at Screening
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
About this study
Official title: Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden
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.
Read the 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.
- Conditions
- Neurofibromatosis 1, NF1, Neurofibromatosis Type 1
- Keywords
- NF1, Plexiform neurofibromas, neurofibromatosis type 1, neurofibromas
- Medical subject headings
- Neurofibromatosis 1, Neurofibroma, Plexiform, Neurofibroma
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine if glucosylceramide (GC) and lactosylceramide (LC) species levels correlate with tumor burden in patients with NF1
The investigator and team will collect blood samples from individuals with NF1 stratified plexiform tumor (PNF) burden (none, small, intermediate, and large) versus age and sex matched healthy control.
Measured: 1 year
Test if tumor burden correlates with GC and LC signature in individuals with NF1 who are undergoing clinical treatment with MEK inhibitors
The investigator and team will enroll 20 individuals with NF1 and inoperable PNFs in treatment with MEK inhibitors to correlate biomarker with tumor burden changes with therapy.
Measured: 1 year
Assemble a longitudinal cohort of individuals with NF1 with plexiform neurofibromas (n=100) for deep phenotyping and tumor burden response to MEK inhibitors
Whole-body MRI at baseline and at time of annual visit (9-to-18-month intervals) will be used to deeply phenotype individuals based on tumor burden and tumor volume. Individuals will undergo plasma collection and clinical history assessment (medications, diet log, supplements, and anthropometric measurements) at each visit. For patients undergoing treatment with MEK inhibitors, a sample prior to treatment will be collected during this study.
Measured: 1 year
Determine if glucosylceramide (GC) and lactosylceramide (LC) signature correlates with plexiform neurofibroma burden change in longitudinal cohort of 100 individuals with PNFs
The investigator and team will test GC/LC levels using validated mass spectrometry target method for quantification of these biomarkers.
Measured: 1 year
Tumor volumetric analysis will be performed to correlate with GC/LC monitoring biomarker signature
GC/LC biomarker thresholds (cut-off) will be refined to evaluate predictive ability to identify individuals with large tumor burden. Tumor burden will be measured from whole-body MRI analysis with post-imaging processing software.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2022
- Study start4 Mar 2022
- Primary completionJun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Children's Hospital Medical Center, Cincinnati
- Responsible party
- Principal investigator, Carlos Prada, MD, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Carlos Prada, MD, Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05238909
- Sponsor's protocol ID
- 2022-4928
- Other IDs
- 7R61NS122094-02, 4R33NS122094-03
- Status last verified
- Sep 2026
- First submitted
- 19 Jan 2022
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Le LQ, Parada LF. Tumor microenvironment and neurofibromatosis type I: connecting the GAPs. Oncogene. 2007 Jul 12;26(32):4609-16. doi: 10.1038/sj.onc.1210261. Epub 2007 Feb 12.
PubMed 17297459McCormick F. Ras signaling and NF1. Curr Opin Genet Dev. 1995 Feb;5(1):51-5. doi: 10.1016/s0959-437x(95)90053-5.
PubMed 7749326Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, Jacks T, Clapp DW, Shannon KM. Nf1 and Gmcsf interact in myeloid leukemogenesis. Mol Cell. 2000 Jan;5(1):189-95. doi: 10.1016/s1097-2765(00)80415-3.
PubMed 10678181Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, Thompson P, Lange BJ, Freedman MH, McCormick F, Jacks T, Shannon K. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet. 1996 Feb;12(2):144-8. doi: 10.1038/ng0296-144.
PubMed 8563751Largaespada DA, Brannan CI, Jenkins NA, Copeland NG. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat Genet. 1996 Feb;12(2):137-43. doi: 10.1038/ng0296-137.
PubMed 8563750Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer. 2015 May;15(5):290-301. doi: 10.1038/nrc3911. Epub 2015 Apr 16.
PubMed 25877329Prada CE, Rangwala FA, Martin LJ, Lovell AM, Saal HM, Schorry EK, Hopkin RJ. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012 Mar;160(3):461-7. doi: 10.1016/j.jpeds.2011.08.051. Epub 2011 Oct 11.
PubMed 21996156Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell. 2008 Feb;13(2):105-16. doi: 10.1016/j.ccr.2007.12.027.
PubMed 18242511Jessen WJ, Miller SJ, Jousma E, Wu J, Rizvi TA, Brundage ME, Eaves D, Widemann B, Kim MO, Dombi E, Sabo J, Hardiman Dudley A, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, Ratner N. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest. 2013 Jan;123(1):340-7. doi: 10.1172/JCI60578. Epub 2012 Dec 10.
PubMed 23221341Jousma E, Rizvi TA, Wu J, Janhofer D, Dombi E, Dunn RS, Kim MO, Masters AR, Jones DR, Cripe TP, Ratner N. Preclinical assessments of the MEK inhibitor PD-0325901 in a mouse model of Neurofibromatosis type 1. Pediatr Blood Cancer. 2015 Oct;62(10):1709-16. doi: 10.1002/pbc.25546. Epub 2015 Apr 22.
PubMed 25907661Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC. Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. N Engl J Med. 2016 Dec 29;375(26):2550-2560. doi: 10.1056/NEJMoa1605943.
PubMed 28029918Dombi E, Solomon J, Gillespie AJ, Fox E, Balis FM, Patronas N, Korf BR, Babovic-Vuksanovic D, Packer RJ, Belasco J, Goldman S, Jakacki R, Kieran M, Steinberg SM, Widemann BC. NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and body weight. Neurology. 2007 Feb 27;68(9):643-7. doi: 10.1212/01.wnl.0000250332.89420.e6. Epub 2007 Jan 10.
PubMed 17215493Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, Weiss B, Kim A, Bornhorst M, Shah AC, Martin S, Roderick MC, Pichard DC, Carbonell A, Paul SM, Therrien J, Kapustina O, Heisey K, Clapp DW, Zhang C, Peer CJ, Figg WD, Smith M, Glod J, Blakeley JO, Steinberg SM, Venzon DJ, Doyle LA, Widemann BC. Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med. 2020 Apr 9;382(15):1430-1442. doi: 10.1056/NEJMoa1912735. Epub 2020 Mar 18.
PubMed 32187457Fletcher JS, Pundavela J, Ratner N. After Nf1 loss in Schwann cells, inflammation drives neurofibroma formation. Neurooncol Adv. 2019 Nov 22;2(Suppl 1):i23-i32. doi: 10.1093/noajnl/vdz045. eCollection 2020 Jul.
PubMed 32642730Fletcher JS, Springer MG, Choi K, Jousma E, Rizvi TA, Dombi E, Kim MO, Wu J, Ratner N. STAT3 inhibition reduces macrophage number and tumor growth in neurofibroma. Oncogene. 2019 Apr;38(15):2876-2884. doi: 10.1038/s41388-018-0600-x. Epub 2018 Dec 12.
PubMed 30542122