Studying Changes Over Time in Patients With Neurofibromatosis Type 1 and Their Healthy Siblings - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00693394

Purpose

RATIONALE: Gathering health information about patients with neurofibromatosis type 1 over time may help doctors learn more about the disease.

PURPOSE: This clinical trial is studying changes over time in patients with neurofibromatosis type 1 and their healthy siblings.

Condition	Intervention
Bone Cancer Brain and Central Nervous System Tumors Precancerous/Nonmalignant Condition Sarcoma	Drug: fludeoxyglucose F 18 Procedure: cognitive assessment Procedure: digital image analysis Procedure: gene expression analysis Procedure: magnetic resonance imaging Procedure: psychosocial assessment and care Procedure: quality-of-life assessment

Genetics Home Reference related topics: familial encephalopathy with neuroserpin inclusion bodies neurofibromatosis type 1 neurofibromatosis type 2

MedlinePlus related topics: Bone Cancer Cancer MRI Scans Neurofibromatosis Soft Tissue Sarcoma

Drug Information available for: Fluorodeoxyglucose F18

U.S. FDA Resources

Study Type:	Observational
Official Title:	Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults With Neurofibromatosis Type 1

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pain and peripheral neuropathy [ Designated as safety issue: No ]
Neuropsychological function [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]
Motor function [ Designated as safety issue: No ]
Endocrinology [ Designated as safety issue: No ]
Cardiopulmonary function [ Designated as safety issue: No ]
Hearing [ Designated as safety issue: No ]
Bony abnormalities [ Designated as safety issue: No ]
Infrequent or unusual NF1 manifestations [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	January 2006
Estimated Primary Completion Date:	January 2018 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To serve as an umbrella protocol for the ongoing neurofibromatosis type 1 (NF1) clinical trials program to longitudinally characterize and analyze NF1-related tumor and non-tumor manifestations and to develop a better understanding of the biology of NF1-related manifestations.
To provide the basis for the development of endpoints for clinical trials and to potentially develop more effective treatments.
To evaluate whole-body tumor burden in children with plexiform neurofibromas (PN) longitudinally.
To analyze growth rate of PN in children and young adults over time.
To evaluate fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) in rapidly growing or painful PN, especially the utility of FDG-PET to differentiate benign PN from malignant peripheral nerve sheath tumors (MPNST).
To analyze the location and growth rate of paraspinal neurofibromas over time using volumetric MRI analysis and 1-dimensional and 2-dimensional measurements.
To evaluate the development and growth rate of dermal neurofibromas using digital photography, volume photography, and digital dermoscopy.
To evaluate the development, number, and size of café-au-lait spots using digital photography, digital dermoscopy, and a colorimeter.
To evaluate the development and number of Lisch nodules longitudinally using slit-lamp examinations.
To evaluate the utility of FDG-PET in the diagnosis of MPNST and in the evaluation of response to chemotherapy, which is not administered as part of this protocol.
To evaluate patients with optic pathway gliomas (OPG) longitudinally by detailed opthalmological examination, proton magnetic resonance spectroscopic imaging (_1H-MRSI), diffusion tensor MRI (DT-MRI), and perfusion MRI.
To evaluate changes in biochemical and metabolic imaging of OPG longitudinally using multivoxel spectroscopy and FDG-PET (on protocol NCI-03-C-0278, principal investigator Kathy Warren, or other subsequent studies as appropriate).
To monitor and evaluate cardiac function at baseline in all individuals and cardiac and pulmonary function longitudinally in individuals with NF1 and clinical findings.
To evaluate hearing at baseline and longitudinally in all individuals and as clinically indicated.
To evaluate individuals longitudinally for scoliosis, other bony abnormalities, bone mineral density, and dental findings.
To evaluate and longitudinally follow patients with NF1 and infrequent or unusual NF1 manifestations.

OUTLINE: This is a multicenter study.

Patients undergo a comprehensive baseline evaluation including clinical phenotyping, genotyping, imaging of tumor manifestations, and pain, quality of life, neuropsychological, motor, and endocrine evaluations. Unaffected siblings (controls) also undergo some of these evaluations.

Skin and tumor manifestations are evaluated with a variety of imaging techniques including digital photography, volume photography, digital dermoscopy, fludeoxyglucose F 18-positron emission tomography (FDG-PET), and MRI. In addition, patients undergo evaluation for pain, neuropsychological function, motor function, and endocrine abnormalities.

Cognitive and social-emotional function are evaluated at baseline and then periodically in patients and unaffected siblings (controls).

Patients are followed for NF1 manifestations periodically ranging from every six months to every three years for approximately 10 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosed with neurofibromatosis type 1 (NF1)* with ≥ 2 or more of the following diagnostic criteria:
- Six or more café-au-lait spots (≥ 0.5 cm in prepubertal subjects or ≥ 1.5 cm in postpubertal subjects)
- At least 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
If participating in the evaluation for variation in gene expression, patient must meet the following criteria:
- Have at least 1 plexiform neurofibroma and be able to undergo MRI analysis of the plexiform neurofibroma(s)
- If possible, 1 or both biologic parents (NF1 affected or not) willing to donate blood or a cheek swab or mouthwash sample NOTE: *NF1 mutation testing to confirm eligibility will not be performed on this protocol but as part of a separate screening study. Histologic confirmation of NF1-related benign tumors is not necessary in the presence of consistent clinical and radiographic findings, but is required for individuals with malignant peripheral nerve sheath tumor (MPNST) who enroll on this study.

PATIENT CHARACTERISTICS:

ECOG 0-3
Must meet 1 of the following age criteria:
- At least 35 years of age for new patients evaluated at NIH
- No upper age limit for patients previously enrolled on clinical trials at NIH or for patients diagnosed with MPNST or with infrequent or unusual NF1-related manifestations
Must be able to obtain an MRI scan
- Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will not be excluded from participation, but will not undergo radiographic evaluations or MRI scans requested for research purposes, or other studies that might negatively impact on the pregnancy

PRIOR CONCURRENT THERAPY:

Prior medical or surgical treatment for NF1 allowed
Concurrent medical and/or radiological treatment for NF1 allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00693394

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Brigitte C. Widemann, MD

NCI - Pediatric Oncology Branch

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000589012, NCI-08-C-0079, NCI-P07283
Study First Received:	June 6, 2008
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00693394
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

bone cancer
precancerous/nonmalignant condition
untreated childhood visual pathway glioma
adult neurofibrosarcoma
childhood neurofibrosarcoma

plexiform neurofibroma
spinal cord neurofibroma
adult pilocytic astrocytoma
adult soft tissue sarcoma
childhood soft tissue sarcoma

Study placed in the following topic categories:

Bone Neoplasms
Precancerous Conditions
Malignant mesenchymal tumor
Bone neoplasms
Central Nervous System Neoplasms
Healthy
Neurodegenerative Diseases
Bone Diseases
Neurofibromatosis 1
Soft tissue sarcomas
Neoplasms, Connective and Soft Tissue
Heredodegenerative Disorders, Nervous System
Musculoskeletal Diseases
Neurofibroma

Neuromuscular Diseases
Glioma
Neurofibroma, Plexiform
Nervous System Neoplasms
Neurocutaneous Syndromes
Astrocytoma
Neurofibromatosis type 1
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neurofibromatoses
Sarcoma
Nerve Sheath Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Nerve Tissue
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009