Clinical trial NCT06515860: Neurofibromatosis Type 1 Tumor Early Detection Study
Official title: Observational Trial of Liquid Biopsy for Malignant Peripheral Nerve Sheath Tumor (MPNST) Among Participants With Neurofibromatosis Type 1
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neurofibromatosis Type 1
Neurofibromatosis 1
Plexiform Neurofibroma
Plexiform Neurofibromas
Malignant Peripheral Nerve Sheath Tumor
Malignant Peripheral Nerve Sheath Tumors
Atypical Neurofibroma
Keywords: Liquid biopsy
Cancer surveillance
Tumor early detection
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2024-07-23
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be adults with NF1 who live in the United States.

Brief summary: The goal of this observational study is to determine if a liquid biopsy (i.e. blood test) is an effective clinical tool for monitoring the development of malignant peripheral nerve sheath tumor (MPNST) among adults (18 years and older) with Neurofibromatosis Type 1 (NF1), compared to the current standard of care. The main questions it aims to answer are:

How effective is liquid biopsy compared to the current standard of care (clinical surveillance and imaging) for early detection of MPNST development among people with NF1? Can liquid biopsy offer a cost-effective method for early detection of MPNST in people with NF1? Also, can liquid biopsy provide earlier detection that potentially leads to better outcomes? Also, can offering liquid biopsy improve access to care for people experiencing barriers to access (such as minority populations or people in rural areas)?

At baseline, participants will be asked to:

* Complete surveys to provide their demographic and NF1-related health information.
* Report whether or not they are experiencing MPNST-related symptoms.
* Provide blood samples (15 mL blood total between three tubes, which is approximately one tablespoon).

Every six months during the five-year follow-up period, participants will be asked to:

* Complete additional surveys to report whether or not they are experiencing MPNST-related symptoms and/or if they have been diagnosed with a new MPNST.
* Provide an additional blood sample (10 mL blood total in one tube).

If diagnosed with an MPNST by their healthcare provider during the follow-up period, participants will be asked to:

* Complete an additional survey regarding their diagnosis and symptoms.
* Provide an additional blood sample (10 mL blood in one tube).
* In parallel, the study team will request a sample of tumor tissue from the care provider, if available.


Eligibility criteria: Inclusion Criteria:

* 18 years and older (adults only)
* Neurofibromatosis Type 1 (NF1) diagnosis (2021 Revised Diagnostic Criteria, PMID: 34012067)
* History of plexiform neurofibroma (PN)
* Able to read and understand English or Spanish
* Live in the USA

Exclusion Criteria:

* Are children (younger than 18 years old)
* Do not have NF1
* Have no evidence of PN
* Are not able to read and understand English or Spanish

Primary outcomes:
measure: Timing of MPNST detection by liquid biopsy
timeFrame: From enrollment to the end of the five-year follow-up period
Secondary outcomes:
measure: Number of participants with new MPNST
timeFrame: From enrollment to the end of the five-year follow-up period
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: David T Miller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miettinen MM, Antonescu CR, Fletcher CDM, Kim A, Lazar AJ, Quezado MM, Reilly KM, Stemmer-Rachamimov A, Stewart DR, Viskochil D, Widemann B, Perry A. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. 2017 Sep;67:1-10. doi: 10.1016/j.humpath.2017.05.010. Epub 2017 May 24.
citation: Klein EA, Richards D, Cohn A, Tummala M, Lapham R, Cosgrove D, Chung G, Clement J, Gao J, Hunkapiller N, Jamshidi A, Kurtzman KN, Seiden MV, Swanton C, Liu MC. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol. 2021 Sep;32(9):1167-1177. doi: 10.1016/j.annonc.2021.05.806. Epub 2021 Jun 24.
citation: Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, Khodadoust MS, Esfahani MS, Liu CL, Zhou L, Scherer F, Kurtz DM, Say C, Carter JN, Merriott DJ, Dudley JC, Binkley MS, Modlin L, Padda SK, Gensheimer MF, West RB, Shrager JB, Neal JW, Wakelee HA, Loo BW Jr, Alizadeh AA, Diehn M. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017 Dec;7(12):1394-1403. doi: 10.1158/2159-8290.CD-17-0716. Epub 2017 Sep 24.
citation: Pemov A, Li H, Presley W, Wallace MR, Miller DT. Genetics of human malignant peripheral nerve sheath tumors. Neurooncol Adv. 2019 Nov 28;2(Suppl 1):i50-i61. doi: 10.1093/noajnl/vdz049. eCollection 2020 Jul.
citation: Cortes-Ciriano I, Steele CD, Piculell K, Al-Ibraheemi A, Eulo V, Bui MM, Chatzipli A, Dickson BC, Borcherding DC, Feber A, Galor A, Hart J, Jones KB, Jordan JT, Kim RH, Lindsay D, Miller C, Nishida Y, Proszek PZ, Serrano J, Sundby RT, Szymanski JJ, Ullrich NJ, Viskochil D, Wang X, Snuderl M, Park PJ, Flanagan AM, Hirbe AC, Pillay N, Miller DT; Genomics of MPNST (GeM) Consortium. Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA. Cancer Discov. 2023 Mar 1;13(3):654-671. doi: 10.1158/2159-8290.CD-22-0786.
citation: Mautner VF, Asuagbor FA, Dombi E, Funsterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008 Aug;10(4):593-8. doi: 10.1215/15228517-2008-011. Epub 2008 Jun 17.
citation: Pemov A, Li H, Patidar R, Hansen NF, Sindiri S, Hartley SW, Wei JS, Elkahloun A, Chandrasekharappa SC; NISC Comparative Sequencing Program; Boland JF, Bass S; NCI DCEG Cancer Genomics Research Laboratory; Mullikin JC, Khan J, Widemann BC, Wallace MR, Stewart DR. The primacy of NF1 loss as the driver of tumorigenesis in neurofibromatosis type 1-associated plexiform neurofibromas. Oncogene. 2017 Jun 1;36(22):3168-3177. doi: 10.1038/onc.2016.464. Epub 2017 Jan 9.