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)

Central Nervous System Neoplasms

All Drugs and Chemicals

Fluorodeoxyglucose F18

Timothy Gershon, MD, PhD

This prospective pilot study is designed to provide preliminary data on the use of Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) in patients with neurofibromatosis-1 (NF1) associated optic glioma and plexiform neurofibroma (PN).

Subjects will undergo FDG-PET-MRI scans in place of standard of care imaging at 0 and 12 months, unless more frequent imaging is clinically indicated. Subjects and their family caregivers will also undergo serial interviews and complete questionnaires related to the psychosocial aspects of NF1.

PET/MRI in CNS and Extra-CNS Tumors of Patients With Neurofibromatosis-1 (NF1)

Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography- Magnetic Resonance Imaging (FDG-PET-MRI) in CNS and Extra-CNS Tumors of Patients With Neurofibromatosis-1 (NF1)

Ratios of SUVmax values within a group of patients who all have progressive disease

SUV max, tumor/brain uptake ratio, tumor/muscle uptake ratio

UNC Lineberger Comprehensive Cancer Center

Glioblastoma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Brain Tumor, Childhood

Anaplastic Astrocytoma

Pilocytic Astrocytoma

Oligoastrocytoma

Antineoplastic Agents

Anti-Infective Agents

Etoposide

Doxorubicin

Liposomal doxorubicin

Etoposide phosphate

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

* MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.
* Participants will undergo DCE and DSC-MRI imaging at the following time points:

  * no more than 3 weeks prior to MLA (OPTIONAL)
  * within approximately 4 days after MLA
  * 2-4 weeks after MLA
  * Every 12 weeks (+/- 7 days) for the first year or until disease progression

* MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.
* Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m\^2 over 5-30 minutes
* Following the completion of doxorubin, etoposide 50 mg/m\^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles)
* Participants will undergo DCE and DSC-MRI imaging at the following time points:

  * no more than 3 weeks prior to MLA (OPTIONAL)
  * within approximately 4 days after MLA
  * 2-4 weeks after MLA
  * every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

MRI-guided laser ablation

Dynamic contrast-enhanced (DCE) MRI

Dynamic susceptibility contrast (DSC) MRI

Margaret Shatara, M.D.

David Limbrick, M.D.

Joshua Shimony, M.D., Ph.D.

Allison King, M.D., M.P.H.

Eric Leuthardt, M.D.

By employing a combination of advanced MRI techniques and correlative serum biomarkers of blood brain barrier (BBB) disruption, the investigators plan to develop a powerful, first of its kind clinical algorithm in pediatrics whereby the investigators can measure and identify the window of maximal BBB disruption post MLA to 1) allow for an alternative to surgery in incompletely resected tumors, 2) allow for optimal chemotherapeutic dosing to achieve the greatest benefits and the least systemic side effects and 3) distinguish subsequent tumor progression from long-term MLA treatment effects. Preliminary data in adult imaging studies have shown that the BBB disruption lasts for several weeks following treatment before returning to a low baseline. This pilot therapeutic study will provide preliminary validation in pediatric patients.

Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors

A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

-Using Karnofsky or Lansky performance status in patients following MLA and in patients who receive doxorubicin and maintenance etoposide after MLA.

The linear regression model will used to investigate the correlation between MR imaging and peritumoral BBB disruption. To account for correlation among the repeated measures from the same patient, the longitudinal data will be analyzed with the use of linear generalized estimating equation (GEE). Whether the average measurements differ at the multiple time points will be evaluated through GEE model. Least-square means at each time points will be presented and standard errors will be calculated within the use of the GEE sandwich method when accounting for within-patient correlation.

Since the investigators do not know which biomarkers will have better correlation with the Ktrans data from DCE and DSC-MRI and patients' survival outcome, the investigators plan to determine the levels of all 3 biomarkers in a blinded fashion. Once both the Ktrans and biomarker levels are available, the investigators will determine which biomarkers have the closest correlation that is statistically significant with the Ktrans. Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority.

Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data (as measured by 6 month PFS rate) to determine whether it has a predictive value.

Washington University School of Medicine

Optic Pathway Glioma

Carboplatin

Vincristine

Endostatins

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Dose of carboplatin is adjusted for age (over 1 year old, full dose, 220 mg/m\^2; 6 months of age or less, 66 percent of the full dose; 7 to 12 months of age, 80 percent).

Dose of vincristine is adjusted for age (over 1 year old, full dose, 1.5 mg/m\^2; 6 months of age or less, 66 percent of the full dose; 7 to 12 months of age, 80 percent). Maximum dose is 2 mg.

Recombinant human endostatin (rh-ES) is administrated at a dose of 15mg daily, for 14 consecutive days every 3 weeks.

Recombinant human endostatin

Jun-ping Zhang

Optic pathway glioma (OPG) can result in visual deterioration. Symptomatic patients often report deficits in visual acuity (VA), visual field, visual-evoked potentials (VEPs), strabismus, proptosis, disc swelling, and other visual/neurological problems. VA itself remains one of the most important outcome measures for OPG patients, with various studies showing strong ties of VA level to overall quality of life and well-being . Maintenance of favorable VA and vision outcomes is of paramount importance in the management of OPG. In terms of management of OPG, surgery and radiotherapy are used on a more limited basis because of location of the tumors and risk of secondary tumors, respectively. Tumor stabilization often prioritized, and chemotherapy is considered ideal for tumor stabilization in OPG, but vision is not always retained and may worsen in some cases, partially due to low radiographic efficacy and long time interval to response of the current chemotherapy regimen.

In the prior study, the investigators modified the traditional carboplatin combined with vincristine regimen by increasing the dose of carboplatin and combining with an anti-angiogenic drug. Of the 15 OPG patients, objective response rate was 80% and the time to response was only 3.3 months. 8 (53%) patients experienced an improvement in visual acuity during therapy and 6 (40%) were stable, which was higher than the historical studies.

This study was launched to further verify the clinical efficacy of the modified regimen and its effect on visual acuity improvement.

Modified CV Regimen in Optic Pathway Glioma

Clinical Study of Modified Carboplatin/Vincristine Chemotherapy Regimen for Visual Function Protection in Children With Optic Pathway Gliomas

Time interval from the beginning of chemotherapy to VA improvement

the percentage of patients who achieved confirmed complete response, partial response or minor response

Time interval from the beginning of chemotherapy to achieving complete response, partial response or minor response

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)
PET/MRI in CNS and Extra-CNS Tumors of Patients With Neurofibromatosis-1 (NF1)	NCT01800032	Neurofibromatos... Optic Glioma Plexiform Neuro...		6 Years -	UNC Lineberger Comprehensive Cancer Center
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)
Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors	NCT02372409	Glioma Pilocytic Astro... Anaplastic Astr... Glioblastoma Mixed Oligoastr... Mixed Glioma Oligodendroglio... Optic Glioma Astrocytoma	MRI-guided lase... Doxorubicin Etoposide Dynamic contras... Dynamic suscept...	3 Years - 21 Years	Washington University School of Medicine
Modified CV Regimen in Optic Pathway Glioma	NCT05278715	Optic Glioma Pediatric Brain...	Carboplatin Vincristine Recombinant hum...	3 Months - 21 Years	Beijing Sanbo Brain Hospital

Spots Global Cancer Trial Database for optic glioma

Every month we try and update this database with for optic glioma cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.