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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-C-0163

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 10 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Fetuses

Keywords

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

Recruitment Keyword(s)

None

Condition(s)

Neurofibromatosis;
MPNST

Investigational Drug(s)

18F FLT

Investigational Device(s)

None

Intervention(s)

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

Supporting Site

National Cancer Institute

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.

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Eligibility

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).


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Citations:

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. Erratum in: Cancer. 2010 Feb 1;116(3):775.

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.

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. Review. Erratum in: Semin Nucl Med. 2008 Mar;38(2):148.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Brigitte C. Widemann, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-3752
10 CENTER DR
BETHESDA MD 20892
(240) 760-6203
widemanb@mail.nih.gov

Brigitte C. Widemann, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-3752
10 CENTER DR
BETHESDA MD 20892
(240) 760-6203
widemanb@mail.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937
ncimo_referrals@mail.nih.gov

Clinical Trials Number:

NCT02211768

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