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

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ClinicalTrials.gov Identifier: NCT02211768
Recruitment Status : Recruiting
First Posted : August 7, 2014
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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.

Condition or disease Intervention/treatment Phase
Neurofibromatosis MPNST Procedure: MRI, FDG-PET/CT scans Procedure: [18F]-FLT-PET/CT scans Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1: Clinical, Histopathologic, and Genomic Analysis
Study Start Date : August 6, 2014
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : July 31, 2019


Arm Intervention/treatment
Experimental: 1
Subjects will undergo FDG-PET and FLT-PET scans at least one day apart
Procedure: MRI, FDG-PET/CT scans
Standard of care to be obtained as part of the study

Procedure: [18F]-FLT-PET/CT scans
FLT PET to be performed as a research imaging study as it is not considered standard imaging in NF1

2
Subjects will undergo FDG-PET scan
Procedure: MRI, FDG-PET/CT scans
Standard of care to be obtained as part of the study

Procedure: [18F]-FLT-PET/CT scans
FLT PET to be performed as a research imaging study as it is not considered standard imaging in NF1




Primary Outcome Measures :
  1. Evaluate the feasibility of wholeexome sequencing and other genetic/genomic methods [ Time Frame: 3 years ]
    Genomic profile of subject's tumors to catalogue mutations associatedwith the development of a PN and then a MPNST

  2. Evaluate the ability of FLT PET to distinguish benign PN from malignant lesions, and to determine if FLT PET is more accurate thanFDG PET in classifying a tumor as benign or malignant [ Time Frame: 3 years ]
    Proportion of patients identified with benign or malignant tumor usingFLT PET versus FDG PET

  3. Determine the feasibility of FLT PET in patients with NF1 and lesionsconcerning for MPNST, or MPNST [ Time Frame: 3 years ]
    Sensitivity of FLT PET in distinguishing benign from malignant lesions



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Ages Eligible for Study:   10 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. 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

      2. 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):

    1. 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)
    2. Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma
    3. Freckling in the axilla or groin
    4. Optic glioma
    5. Two or more Lisch nodules
    6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
    7. A first-degree relative with NF1

    3. NFI tumor manifestations

Subjects must have:

  1. Diagnosis of NF1 with a lesion concerning for MPNST

    -Criteria include pain, growth of a known plexiform neurofibroma, abnormality on functional imaging study (FDG-PET) or change in clinical exam.

    OR

  2. Diagnosis of NF1 with a histologically confirmed MPNST.

4. Subjects must be eligible for and willing to participate and sign consent for NCI protocol 08-C-0079: Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type 1, for the clinical evaluation necessary for this study.

5. Prior and current therapy:

For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment. Chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors. For the purpose of this study subjects who have not previously received medical or surgical treatment, patients who have previously received medical or surgical treatment, and subjects who are currently receiving medical treatment and or radiation for a NF1 related manifestation will be eligible.

Patients must be recovered from acute toxicities of prior therapy in order to be able to safely undergo biopsies proposed on the trial. Prior and current treatment for NF1 related manifestations will be recorded on protocol 08-C-0079.

Prior radiation therapy and chemotherapy in patients with MPNST must not have been administered within 4 weeks prior to enrollment.

6. Performance Status:

ECOG less than or equal to 3. Subjects who are wheelchair bound because of paralysis will be considered ambulatory when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations.

7. Informed Consent:

All patients or their legal guardians (if the patients is<18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.

8. Hematologic criteria (applicable only in patients undergoing biopsy)

  • Platelet count has to be greater than or equal to 100,000/microL
  • Patients should have INR<1.4 and PT less than or greater to 40 seconds (unless due to lupus anticoagulant). In patients not meeting these parameters, clearance by hematology will be required prior to undergoing biopsy.

EXCLUSION CRITERIA:

  1. Allergy or relative contraindications to MRI contrast agents.
  2. 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.
  3. 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.
  4. Patients with severe chronic renal insufficiency (glomerular filtration rate < 30 mL/min/1.73 m(2)), hepatorenal syndrome or post-liver transplantation.
  5. History of prior fluorothymidine allergy or intolerance.
  6. Participants with severe claustrophobia not relieved by oral anxiolytic medication or patients weighing >136 kg (weight limit for scanner table)
  7. 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.
  8. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02211768


Contacts
Contact: Jessica G Caidor, R.N. (301) 594-4762 jessica.caidor@nih.gov
Contact: Brigitte C Widemann, M.D. (240) 760-6203 widemanb@pbmac.nci.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Brigitte C Widemann, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02211768     History of Changes
Other Study ID Numbers: 140163
14-C-0163
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 11, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Genetic Analysis
Biopsy
FDG-PET
FLT-PET

Additional relevant MeSH terms:
Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Nerve Sheath Neoplasms
Neurofibroma, Plexiform
Neurilemmoma
Neurofibrosarcoma
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
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma