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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1: Clinical, Histopathologic, and Genomic Analysis

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. Res

    Detailed Summary:

    Background:

    • NF1 is an autosomal dominant genetic disorder characterized by distinct features including the development of benign plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumors (MPNST) tumors of the nervous system.
    • Development of MPNST typically results from malignant transformation in a preexisting PN. Associated symptoms may overlap and be difficult to distinguish from growth of a benign PN. Currently surgery is the only standard treatment for PN and MPNST.
    • The 5-year overall survival rate for NF1 patients with a MPNST is poor; therefore, early detection of malignant transformation of a PN is an important goal.
    • Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) in NF1 has utility in detecting malignant transformation. However, concerning lesions can have high FDG uptake and be benign on biopsy.
    • Fluoro-thymidine (FLT) PET measures cell cycling and proliferation. Malignant lesions have higher proliferation rates than benign tumors; therefore, FLT-PET may be sensitive and specific in the early detection of malignant transformation and assess response.
    • Genetic analysis is an important component in evaluating the transformation of PN to MPNST. Biallelic NF1 and tumor suppressor gene mutations (p53, INK4A, p27kip1), increased Ras activity and abnormal growth factor signaling have been described, but there is no known signature for MPNST.
    • Massively parallel ( next generation ) sequencing technology permits whole-genome, whole-exome and transcriptome sequencing of multiple tumors including MPNST.

    Objectives:

    • Feasibility [ Time Frame: 3 years ]
    • Ability to distinguish lesions and accuracy [ Time Frame: 3 years ]
    • Feasibility of whole-exome sequencing [ Time Frame: 3 years ]


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Clinical analysis for NF1/MPNST [ Time Frame: 3 years ]
    • Pathological analysis [ Time Frame: 3 years ]
    • Identify somatic genetic variants [ Time Frame: 3 years ]


    Original Secondary Outcome: Same as current

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: August 6, 2014
    Date Started: August 1, 2014
    Date Completion: July 1, 2018
    Last Updated: May 12, 2017
    Last Verified: April 17, 2017