Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1

NCT02211768 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14016314-C-0163
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background:\<TAB\> \- Many people with neurofibromatosis type 1 (NF1) get tumors of the nervous system. Finding malignant tumors early is important for removing them. Researchers want to find ways of doing this with scans and genetic testing. Objectives: \- To learn more about neurofibromatosis type 1. Eligibility: \- People age 10 and older with NF1 who have a benign tumor or have had a malignant one. Design:

• Participants will be screened in another study with medical history, physical exam, and urine and blood tests. They will have a magnetic resonance imaging (MRI) scan.
• MRI: Participants will lie on a table that slides into a metal cylinder. They will be in the scanner for 60 90 minutes, lying still for 15 minutes at a time. Participants will get earplugs for the loud sounds. They will get a contrast agent (dye) through a thin plastic tube (catheter) inserted in an arm vein.
• As part of their regular care, participants will have:
• FDG-PET/CT scan. They will get radioactive glucose (sugar) through a catheter in an arm vein.
• \[18F\]-FLT-PET/CT scan. This is like the FDG scan but with a different radioactive chemical.
• Biopsy. A piece of tumor tissue is removed with a needle. A piece of tissue from a previous biopsy may also be studied.
• Participants may have genetic testing. Blood will be taken. It will be tested along with biopsy samples. Researchers will explain the risks and procedures. They may notify participants if testing shows health problems.
• After this study, participants will continue their regular cancer care.

Conditions

MPNST; Neurofibromatosis

Keywords

Genetic Analysis; Biopsy; FDG-PET; FLT-PET

Outcome Measures

Primary Outcomes (3)

• Evaluate the feasibility of whole-exome sequencing and other genetic/genomic methods

  Genomic profile of subject's tumors to catalogue mutations associated with the development of a PN and then a MPNST

  3 years

• Evaluate the ability of FLT PET to distinguish benign PN from malignant lesions, and to determine if FLT PET is more accurate than FDG PET in classifying a tumor as benign or malignant

  Proportion of patients identified with benign or malignant tumor using FLT PET versus FDG PET

  3 years

• Determine the feasibility of FLT PET in patients with NF1 and lesions concerning for MPNST, or MPNST

  Sensitivity of FLT PET in distinguishing benign from malignant lesions

  3 years

Study Arms (2)

1/FDG and FLT PET scans

EXPERIMENTAL

Subjects will undergo FDG-PET and FLT-PET scans at least one day apart

Procedure: MRI, FDG-PET/CT scans; Drug: [18F]-FLT-PET/CT scans

2/FDG-PET scan

OTHER

Subjects will undergo FDG-PET scan

Procedure: MRI, FDG-PET/CT scans

Interventions

MRI, FDG-PET/CT scans PROCEDURE

Standard of care to be obtained as part of the study

1/FDG and FLT PET scans; 2/FDG-PET scan

[18F]-FLT-PET/CT scans DRUG

FLT PET to be performed as a research imaging study as it is not considered standard imaging in NF1

1/FDG and FLT PET scans

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age:
• No upper age limit for patient enrollment.
• FLT PET: will only be performed in patients greater than or equal to 10 years old
• Research biopsies in consenting patients with MPNST: will only be performed in patients greater than or equal to 18 years old
• \. Diagnosis:
• Patients who are diagnosed with NF1 using the NIH Consensus Conference criteria or have a confirmed NF1 mutation with analysis performed in a CLIA certified laboratory. NF1 mutation testing to confirm eligibility will not be performed on this protocol, but as part the POB separate screening study.
• For the clinical diagnosis of NF1 all study subjects must have at two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):
• Six or more caf(SqrRoot)(Copyright)-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects)
• Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma
• Freckling in the axilla or groin
• Optic glioma
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A first-degree relative with NF1
• \. NFI tumor manifestations

You may not qualify if:

• Allergy or relative contraindications to MRI contrast agents.
• Patients who require sedation for imaging studies will be excluded from the FLT PET scan research test. They will undergo only the standard of care MRI and FDG PET scan.
• Contraindication to MRI scanning, such as surgery that involves metal clips or wires or metal prostheses which might be expected to cause tissue damage or produce image artifacts.
• Patients with severe chronic renal insufficiency (glomerular filtration rate \< 30 mL/min/1.73 m(2)), hepatorenal syndrome or post-liver transplantation.
• History of prior fluorothymidine allergy or intolerance.
• Participants with severe claustrophobia not relieved by oral anxiolytic medication or patients weighing \>136 kg (weight limit for scanner table)
• Pregnant women are excluded from this study because of the effects of radioactive materials with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with radioactive materials, breastfeeding should be discontinued.
• Requirement for medications, which interfere with platelet function, such as aspirin, which cannot be stopped within 1 week prior to the biopsy (applicable only to patients undergoing biopsy).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Benz MR, Czernin J, Dry SM, Tap WD, Allen-Auerbach MS, Elashoff D, Phelps ME, Weber WA, Eilber FC. Quantitative F18-fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign. Cancer. 2010 Jan 15;116(2):451-8. doi: 10.1002/cncr.24755.

  PMID: 19924789 BACKGROUND

• Meany H, Dombi E, Reynolds J, Whatley M, Kurwa A, Tsokos M, Salzer W, Gillespie A, Baldwin A, Derdak J, Widemann B. 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) evaluation of nodular lesions in patients with Neurofibromatosis type 1 and plexiform neurofibromas (PN) or malignant peripheral nerve sheath tumors (MPNST). Pediatr Blood Cancer. 2013 Jan;60(1):59-64. doi: 10.1002/pbc.24212. Epub 2012 May 29.

  PMID: 22645095 BACKGROUND

• Salskov A, Tammisetti VS, Grierson J, Vesselle H. FLT: measuring tumor cell proliferation in vivo with positron emission tomography and 3'-deoxy-3'-[18F]fluorothymidine. Semin Nucl Med. 2007 Nov;37(6):429-39. doi: 10.1053/j.semnuclmed.2007.08.001.

  PMID: 17920350 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatoses; Neurofibrosarcoma

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2014
• First Posted: August 7, 2014
• Study Start: December 8, 2014
• Primary Completion: September 5, 2017
• Study Completion: December 30, 2019
• Last Updated: April 29, 2026

Record last verified: 2025-07-23

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)