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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT02211768
• Date of registration: 06/08/2014
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1
• Scientific title: Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1: Clinical, Histopathologic, and Genomic Analysis
• Date of first enrolment: December 8, 2014
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02211768
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Diagnostic. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Brigitte C Widemann, M.D.
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion 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).



Age minimum: 10 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

MPNST

Neurofibromatosis

Intervention(s)

Procedure: MRI, FDG-PET/CT scans

Drug: [18F]-FLT-PET/CT scans

Primary Outcome(s)

Determine the feasibility of FLT PET in patients with NF1 and lesions concerning for MPNST, or MPNST [Time Frame: 3 years]

Evaluate the feasibility of whole-exome sequencing and other genetic/genomic methods [Time Frame: 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 [Time Frame: 3 years]

Secondary ID(s)

14-C-0163

140163

Source(s) of Monetary Support

Please refer to primary and secondary sponsors