Neoplasms

All Conditions

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Eye Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Glioma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Nerve Sheath Neoplasms

Neurofibrosarcoma

Optic Nerve Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Optic Nerve Neoplasms

Cranial Nerve Diseases

Optic Nerve Diseases

Neurofibromatosis

Neurofibromatosis Type 1

Malignant Peripheral Nerve Sheath Tumor

Neuroepithelioma

Soft Tissue Sarcoma

Biologic parents of children and adults with NFI will be evaluated at one time point, using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment

Children and adults with NFI whose tumor and non tumor related manifestations will be longitudinally evaluated. Closed to enrollment

Unaffected siblings of children and adults with NFI will be evaluated at one time point using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment

Brigitte C Widemann, M.D.

Background:

Neurofibromatosis Type 1 (NF1) is a genetic disorder in which patients are at increased risk of developing tumors (usually non-cancerous) of the central and peripheral nervous system. The disease affects essentially every organ system.

The natural course of NFI over time is poorly understood. For most patients the only treatment option is surgery. A better understanding of NF1 may be helpful for the design of future treatment studies.

Objectives:

To evaluate people with NF1 over 10 years in order to better understand the natural history of the disease.

To characterize the patient population and to examine how NFI affects patients quality of life and function.

Eligibility:

Children, adolescents, and adults with NF1.

Design:

Participants have a comprehensive baseline evaluation including genetic testing, tumor imaging, pain and quality-of-life assessments, and neuropsychological, motor and endocrine evaluations.

Patients are monitored every 6 months to every 3 years, depending on their individual findings at the baseline study. Tests may include the following, as appropriate:

* Medical history, physical examination and blood tests.
* Whole body and face photography to monitor visible deformities.
* Neuropsychological testing, quality-of-life evaluations, motor function tests, endocrinologic evaluations, heart and lung function tests, hearing tests, bone density scans and other bone evaluations.
* MRI and PET scans to detect and assess plexiform neurofibromas (tumors that arise from nerves and can cause serious problems), paraspinal neurofibromas (tumors that arise from nerves around the spine and can cause problems by compressing the spinal cord), and malignant peripheral nerve sheath tumors (a type of cancer that arises from a peripheral nerve or involves the sheath covering the nerve).
* Eye exams, MRI scans and PET scans to evaluate optic pathway gliomas (tumors arising from the vision nerves or the brain areas for vision) and the chemicals within the tumor and brain.
* Eye exams and photographs to evaluate the development of Lisch nodules (non-cancerous tumors on the eye).
* Photographs of dermal neurofibromas (tumors of the skin), cafe-au-lait spots (dark or pigmented areas on the skin that are often the first signs of NF1) and other skin problems.
* Pain evaluations to monitor the different types of pain patients experience, causes of the pain, how often the pain occurs, effect of the pain on quality of life, and what pain medications and alternative treatments, such as acupuncture, are effective.

Background

Neurofibromatosis Type 1 (NF1) is an autosomal dominant, progressive genetic disorder characterized by diverse clinical manifestations. Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas (PN), dermal neurofibromas, optic pathway tumors, brain tumors, malignant peripheral nerve sheath tumors (MPNST), juvenile myelomonocytic leukemia, and pheochromocytomas. In addition, NF1 manifests in essentially every organ system, with for example, skeletal and vascular abnormalities, and cognitive deficits. Thus, the care for individuals with NF1 requires a multidisciplinary approach. The natural history of NF1 related tumor and other manifestations is poorly understood, and for most NF1 related tumor manifestations the only standard treatment option is surgery. The NIH Clinical Center provides the ideal infrastructure for evaluation of the natural history of rare diseases. A better understanding of the natural history of NF1 related tumor and other manifestations will be helpful for the design of treatment studies. The NCI, POB has an active clinical trials program for NF1 related tumor manifestations including PN, MPNST. Unlike individuals with refractory solid cancers, individuals with NF1 have near normal life expectancy, and their benign tumors progress more slowly than solid cancers. Individuals with NF1 may thus participate in multiple treatment trials.

Objectives

The overall purpose of this descriptive NF1 Natural History study is to serve as an umbrella protocol for the ongoing NF1 clinical trials program to allow the longitudinal evaluation of individuals with NF1 for NF1 related tumor and non tumor manifestations irrespective whether they are currently enrolled on a treatment study or not, and to develop a better understanding of the biology of NF1 related manifestations. Following these patients longitudinally will allow investigators to develop a better understanding of the natural history of these manifestations, provide the basis for the development of endpoints for clinical trials and to potentially develop more effective treatments. NF1 manifestations, which will be followed longitudinally, include PN, MPNST, optic pathway tumors, dermal neurofibromas, NF1 associated pain, and neuropsychological, motor, and endocrine function. Patient samples will be collected to investigate the existence of a peripherally detectable disease progression biomarker. A comprehensive treatment plan and recommendations will be developed and communicated with the patient and primary caregivers.

Eligibility

Children, adolescents, and adults with a confirmed clinical diagnosis of NF1 or a confirmed NF1 mutation.

Design

Attempts will be made to have all individuals undergo a comprehensive baseline evaluation including clinical phenotyping, genotyping, imaging of tumor manifestations, and pain, quality of life, neuropsychological, motor, and endocrine evaluations. The NF1 manifestations will be longitudinally monitored with a frequency of every year to every three years, with the extent and timing of follow-up evaluations depending on the findings at baseline.

Natural History Study of Patients With Neurofibromatosis Type I

Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults With Neurofibromatosis Type 1

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Characterized features will be described and presented.

National Cancer Institute (NCI)

Meningioma

Atrophy

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Conformal focal-brain irradiation using modern radiotherapeutic techniques (i.e., conventionally fractionated VMAT, hypofractionated stereotactic radiotherapy, and proton beam therapy, etc)

The techniques of conformal focal-brain irradiation in the era of modern radiotherapy (i.e., conventionally fractionated VMAT, hypofractionated stereotactic radiotherapy, and proton beam therapy, etc)

Radiation

Chi-Cheng Chuang, M.D.

Shinn-Yn Lin, M.D.

【Background】For cranial-irradiation-naive patients with intracranial meningiomas at risk of local recurrence, the administration of conformal cranial radiotherapy can enhance tumor control in the current era of modern radiotherapeutic techniques. Life expectancy in patients with intracranial meningiomas, particularly non-malignant meningiomas (WHO grade I and II) is essentially similar to people of general population. However, RT-related neurocognitive function (NCF) sequelae are potentially and seriously a concern which should not be ignored. In terms of the natural course of cranial irradiation-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline principally involves impairments of episodic memory, which is significantly associated with functions of the hippocampus. Additionally, the extent of changes in hippocampal volume after local irradiation may be associated with the hippocampal dosimetry. This study thus aims to investigate the potential cause-effect relationship between the hippocampal dosimetry and radiological outcomes represented by the volumetric changes regarding the contralateral hippocampus; furthermore, the correlation between radiological outcomes and neurocognitive endpoints will be examined and clarified.

【Methods】Patients with cranial-RT-naive intracranial meningiomas may be eligible and therefore enrolled in this prospective study addressing both radiological outcomes and neurocognitive endpoints. All eligible and recruited patients should receive baseline volumetric brain MRI examination and baseline neurobehavioral assessment. Subsequently, conformal cranial irradiation in the era of modern radiotherapeutic techniques (including hypofractionated stereotactic radiotherapy, proton beam therapy volumetric modulated arc therapy) will be utilized in order to reduce the dose irradiating the contralateral hippocampus and other relevant organs at risk. The prescribed dose schemes for treating patients with intracranial meningioma depend on the decision of the radiation oncologist in charge and follow the treatment guidelines at our cancer center. Accordingly, a battery of neurocognitive measures, which includes 9 standardized neuropsychological tests categorized into 5 NCF domains (e.g., executive functions, verbal \& non-verbal memory, working memory, psychomotor speed, and amygdala-related emotion recognition), is used to evaluate neurocognitive performances longitudinally for our registered patients. There will be two co-primary outcome measures in the current study. The main primary outcome will be the correlation between the mean hippocampal dose and the extent of change in hippocampal volume at 6 months after the course of cranial RT. The other primary endpoint will be 6-month cognitive-deterioration-free survival.

【Expected Results】This prospective observational cohort study aims to explore and investigate the cause-effect relationship between the hippocampal dosimetry (i.e., mean dose irradiating the hippocampus, particularly the one contralateral to the lateralization of intracranial meningioma) and the extent of hippocampal atrophy signifying one of the measures regarding radiological outcomes. Simultaneously, predefined standardized neurocognitive outcome measures such as hippocampus-related memory functions and amygdala-related emotion recognition will be obtained prospectively and longitudinally in order to examine whether any meaningfully significant correlation exists between the above radiological outcome measures and neurocognitive endpoints. The mutual associations among hippocampal dosimetry, radiological outcomes including the MRI-delineated hippocampal volume, and neurocognitive endpoints including hippocampus-related verbal/non-verbal memory functions will be examined thoroughly.

Cognition-preserving Brain Irradiation for Treating Patients With Intracranial Meningioma in the Era of Modern Radiotherapeutic Techniques Including Proton Beam Therapy - a Prospective Study Focusing on Radiological Outcomes and Neurocognitive Endpoints

Longitudinal changes in the volumes (cc) of the left hippocampus, right hippocampus, left amygdala, right amygdala, left thalamus, right thalamus, and so on based on volumetric MR imaging examinations

Change in verbal memory function related to left hippocampus from baseline to 4 months after cognition-preserving cranial RT

Change in non-verbal memory learning associated with right hippocampus from baseline to 4 months after cognition-preserving brain RT

Change in executive function related to hippocampus from baseline to 4 months after cognition-preserving cranial RT.

Concerning the domain of executive functions generally dominated by the frontal lobes, the Modified Card Sorting Test is employed to assess both conceptual formation and mental shifting which have been documented to be the major components of executive functions.

Change in emotion memory tasks associated with the amygdala from baseline to 4 months after cognition-reserving cranial irradiation.

For evaluate and quantify the cognitive function of amygdala, the NCF test tailored to the emotional recognition task will be used and patients' performances will be assessed using the commercialized and computerized test included in Cambridge Cognition® package.

Change in working memory related to hippocampus from baseline to 4 months after cognition-preserving cranial RT.

Working memory includes executive functions and psychomotor speed.

* The neurocognitive outcome of verbal working memory was determined by the Digit Span Subtest (DS) and Spatial Span (SSP) of the Wechsler Adult Intelligence Scale- 3rd edition (WAIS-III®).
* In order to indicate patients' performance on the psychomotor speed, we make use of Psychomotor Speed Index (PSI), which is derived from the composite score of Digit Symbol Coding Subtest (DSS) and Symbol Searching Subtest (SS) of the WAIS-III®.

Longitudinal changes in the imaging biomarkers from DTI imaging

Longitudinal changes in the fractional anisotropy (FA, unitless index between 0 and 1) from DTI imaging

Trajectories in the imaging biomarker, mean diffusivity (MD, mm squared/second) based on DTI imaging

Chang Gung Memorial Hospital

Background:

-Plexiform neurofibromas in patients with NF1 are a significant cause of morbidity but little is known about the natural history of these lesions.

Objectives:

* The purpose of this study is to monitor the natural history of plexiform neurofibromas and to evaluate the usefulness of volumetric MRI tumor measurements in this disease.
* Other goals of the study are to provide a body of normative data on the growth rate of plexiform neurofibromas and to establish a tissue repository and pathology review center to allow future studies of the pathogenesis of neurofibromas and clinical trials of potential therapeutic agents.

Design

- This study is coordinated by Dr. Bruce Korf, and was initiated when he was at the Partners Center for Human Genetics, Boston, MA.

Study of Plexiform Neurofibromas in Neurofibromatosis Type 1

Natural History of Plexiform in Neurofibromatosis Type I

Monitor natural history of plexiform neurofibromas

Usefulness of volumetric MRI measurements

orally 50 mg/dose, every 12 hours every day continuously (1 cycle = 28 days)

Selumetinib

Background:

Neurofibromatosis type 1 (NF1) is a disorder that can cause plexiform neurofibromas (PNs). These are tumors that grow along nerves. Some PNs cause serious health problems. PNs often can t be operated on because of their large size, location, or number. There are no effective treatments known for people with NF1 and PNs. Researchers want to test if the drug selumetinib (AZD6244 hydrogen sulfate) causes PNs to shrink or slows down their growth.

Objectives:

To test if selumetinib helps treat PNs. To test how the body handles selumetinib and how it affects peoples symptoms.

Eligibility:

People ages 18 and older with NF1, with an inoperable PN that causes morbidity or is growing

Design:

Participants will be screened with:

Medical history and physical exam

Blood, urine, and heart tests

Eye exam

MRI: They lie in a machine that takes pictures of the body.

PN biopsy: A small piece of the tumor is removed by a large needle.

Questionnaires

Participants will swallow selumetinib capsules every 12 hours for several 28-day cycles. The capsules are taken with a full glass of water on an empty stomach. Participants may have only water for 2 hours before and 1 hour after each dose.

Participants will keep a drug diary. They will continue taking the drug as long as they tolerate it and their disease doesn t progress.

Participants will have several visits throughout the study. These will include repeats of the screening tests.

Participants will have a final visit after they stop taking selumetinib.

Background:

* Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with an incidence of 1:3500 in the US. One of the cardinal features of NF1 is the development of histologically benign peripheral nervesheath tumors called plexiform neurofibromas (PN) in 25-40% of individuals with NF1. Unlike discrete neurofibromas, PN grow along the length of nerves and involve multiple branches of a nerve. They are a major source of morbidity, causing disfigurement, impairment of nerve function, pain, and in some cases development of malignant peripheral nerve sheath tumors.
* Selumetinib (AZD6244) is a novel orally bioavailable mitogen activated protein kinase inhibitor, is a specific inhibitor of MEK 1/2, which may mediate anti-tumor effects in PN by inhibition of downstream signaling of Ras. Selumetinib is currently undergoing evaluation in adult cancers and children with brain tumors and NF1-related plexiform neurofibromas.
* In an NCI phase I trial of selumetinib for children and young adults with NF1 and inoperable PN we have observed preliminary activity with PN volume decrease in \>50% of patients enrolled. This degree of activity has not been observed in prior trials directed at PN. While preliminary activity has been seen in most patients enrolled to date, in several patients who required (Bullet) 1 dose reduction for toxicity, after an initial volume decrease, the PN volumes appear to be increasing slowly, and in one patient a nodular appearing lesion is not responding to selumetinib. These findings suggest that not all PN types may be responsive to selumetinib and that a certain selumetinib tissue concentration may be required for target inhibition and anti-tumor activity.

Objective:

-Determine the objective response rate (PN volume decrease greater than or equal to 20% compared to baseline) to selumetinib in adult patients with inoperable PN.

Eligibility:

* Patients must be at least 18 years of age with a diagnosis of NF1, with an inoperable, measureable PN that causes morbidity or is growing, which is amenable to percutaneous biopsy, and must be willing to undergo two biopsies.
* Up to 10 patients who meet all criteria, but have PN, which cannot be biopsied safely, will be eligible for the treatment portion of the study.
* Patients must have adequate organ function, be able to undergo serial MRI scans and have recovered from acute toxicity of all prior treatment.

Design:

* This is a single site open label phase II study in which all subjects will receive selumetinib orally approximately every 12 hours until patient develops progression of disease, unacceptable toxicity or, in patients with non-progressive, symptomatic PN at enrollment, a maximum of 2 years (unless they experience a partial response, or an improvement in symptoms or function in which case they may continue until progression of disease).
* Selumetinib will be administered at a dose of 50 mg BID on a continuous dosing schedule (1 cycle=28 days), which is the recommended adult dose. A maximum accrual of 35 evaluable patients to meet the primary objective; while a maximum of 60 patients in total may be enrolled to allow for a small number of screen failures, inevaluable patients and up to 10 patients who cannot safely undergo two biopsies of PNs. Enrollment will proceed over approximately 24 months.

MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas

Phase II Trial of the MEK1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas

.All collected IPD will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request.

Evaluate immune infiltrate of PN and Peripheral blood for circulating tumor cells

Evalaute change in dermal neurofibroma by photography

Time to progression and progression free survival

Correlate 3D MRI responses with % target inhibition of pERK in PN biopsies

Compare pERK inhibition in dermal neurofibromas and PN

Characterize effects on pain, quality of life, physical functioning

Analyze paired biopsies with mechanisms of response and resistance

Analyze bone marrow derived precursor cells and cytokines before and after treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Natural History Study of Patients With Neurofibromatosis Type I	NCT00924196	Neurofibromatos... Malignant Perip... Plexiform Neuro... Optic Glioma Neurofibroma		4 Weeks -	National Institutes of Health Clinical Center (CC)
Cognition-preserving Brain Irradiation for Treating Patients With Intracranial Meningioma in the Era of Modern Radiotherapeutic Techniques Including Proton Beam Therapy - a Prospective Study Focusing on Radiological Outcomes and Neurocognitive Endpoints	NCT05832099	Intracranial Me...	Radiation	18 Years - 85 Years	Chang Gung Memorial Hospital
Natural History Study of Patients With Neurofibromatosis Type I	NCT00924196	Neurofibromatos... Malignant Perip... Plexiform Neuro... Optic Glioma Neurofibroma		4 Weeks -	National Institutes of Health Clinical Center (CC)
Study of Plexiform Neurofibromas in Neurofibromatosis Type 1	NCT00006435	Plexiform Neuro... NF1		- 100 Years	National Institutes of Health Clinical Center (CC)
MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas	NCT02407405	Neurofibromatos... Plexiform Neuro...	Selumetinib	18 Years -	National Institutes of Health Clinical Center (CC)
MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas	NCT02407405	Neurofibromatos... Plexiform Neuro...	Selumetinib	18 Years -	National Institutes of Health Clinical Center (CC)

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