Clinical Research Directory

Development of Patient-Reported Outcome Measures Assessing Tumor Visibility and Appearance Concerns in Neurofibromatosis Type 1: A Qualitative Study

Background: Neurofibromatosis 1 (NF1) is a disease that causes tumors to grow along the nerves. These include plexiform neurofibromas (pNF) and cutaneous neurofibromas (cNF). Both pNF and cNF can be visible to other people. These tumors can affect a person s appearance and quality of life. Researchers want to be able to assess changes in appearance before and after treatment for NF1 tumors. Objective: To see if two questionnaires can help assess people s ratings about the appearance of their pNF and cNF tumors. Eligibility: People aged 8 years and older with pNF and people 12 years and older either with cNF or both pNF and cNF. Adult caregivers of children with pNF and cNF are also needed. Design: Participants will complete questionnaires on paper or by phone, computer, or tablet. They will answer questions about how they look, how they feel, and how they feel about the way they look. Participants will meet in at least 1 remote focus group or individual interview. The meeting will last about 1 hour. Each group will include 3 to 5 people, organized by age: 8 to 11 years, 12 to 17 years, 18 to 29 years, and over 30 years. Adult caregivers will meet in a group with other caregivers. They will discuss their NF1 symptoms; how their tumors look; how they feel about the way their tumors look; and their daily activities. They will give their opinions about 2 questionnaires about appearance. The group and individual meetings will be audio-recorded and transcribed. Information that can reveal individual identities will be removed.

A Study to Evaluate the Feasibility of a Physiologic Biomarker to Assess Pain and Other Sensory Problems Using Pupillometry in Participants With Neurofibromatosis Type 1 (NF1)

Background: Neurofibromatosis type 1 (NF1) is a genetic condition that causes tumors to grow along the nerves in the skin, brain, and other parts of the body. People with NF1 often have pain and may experience other abnormal sensations like itching, numbness, or tingling. These symptoms can affect their daily life. Researchers want to learn more about these symptoms and find better ways to measure pain in people with NF1. Objective: To learn if a device called the AlgometRx Nociometer(Registered trademark) is effective in measuring pain or other abnormal sensations in people with NF1. Eligibility: People aged 1 year and older with NF1. Design: Individuals can have up to 3 assessments completed in person. Each assessment may last up to 1.0 to 1.5 hours. Individuals will be screened. They will complete questionnaires about their health and how bad their pain is. If participants are having blood drawn for other reasons, some additional samples may be used in this study. The AlgometRx Nociometer includes an electrode that will be placed onto a finger or a toe. The electrode will send non-painful electrical signals to activate nerves in the finger or toe. At the same time, a camera will be used to record changes in the pupil of the eye. The test will be done on all 4 of the participant s limbs; however, researchers may skip 1 or more limbs for various reasons. This test takes about 10 seconds to complete with at least a one-minute rest between testing different limbs. Individuals will be asked to do a 2nd assessment with the AlgometRx Nociometer that may be done 1 hour later but no more than 72 hours after the first assessment. Participants who will be returning for another visit can opt to do a 3rd assessment that will be done at least 4 weeks but not more than 18 months after the 1st....

A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma

This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Chemotherapy drugs, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.

Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Pediatric Long-Term Follow-up and Rollover Study

A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors

Background: \- Plexiform neurofibromas are tumors that grow in and around nerves. The only way to treat them is with surgery. Some of these tumors cannot be completely removed. The tumors may be too large, too numerous, or in a bad location for surgery. An experimental drug called AZD6244 hydrogen sulfate may be able to prevent the tumors from growing, slow down their growth, or shrink them. This drug has been tested in adults with cancer and in children with some types of brain cancer. This study will test how well this drug works with these types of tumors. Objectives: \- To study the safety and effectiveness of AZD6244 hydrogen sulfate in children and young adults with plexiform neurofibromas that cannot be completely removed by surgery. Eligibility: \- Children and young adults between 12 and 18 years of age who have plexiform neurofibromas that cannot be completely removed by surgery. Design: * Patients will be screened with a physical exam, medical history, blood tests, and imaging studies. * They will take the study drug twice a day with 8 ounces of water, every day for 28-day cycles of treatment. During study visits, participants will have blood and urine tests and physical exams. They will also have imaging studies to examine the tumor sizes and locations. They will answer questions about their health. They may have other tests as needed. * Participants will continue to receive the study drug as long as they have no severe side effects and the disease is not getting worse.

Natural History Study of Patients With Neurofibromatosis Type I

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.

A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1

The trial will be an open label, single arm, phase 2 study to assess the tolerability and efficacy of HLX-1502 in participants with NF1 that are 16 years or older in age with progressive and/or symptomatic PN. This study will also investigate the safety and efficacy of HLX-1502 in a small cohort of 12 to 15 year olds.

PASS of Paediatric Patients Initiating Selumetinib

Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant genetic disorder that is caused by germline mutations in the NF1 tumour suppressor gene, which encodes the tumour suppressor protein neurofibromin 1. Plexiform neurofibromas (PN) are histologically benign nerve sheath tumours, which typically grow along large nerves and plexi. On 5 March 2020, a centralised Marketing Authorisation Application was submitted to the European Medicines Agency (EMA), Marketing Authorisation in EU was granted on 17 Jun 2021. As part of the approval process, a Risk Management Plan (RMP) was developed and submitted to the EMA to summarise the safety concerns emerging from the clinical development program. The RMP included additional pharmacovigilance plans for a noninterventional Post-authorisation Safety Study (PASS) to further characterise the safety of selumetinib in paediatric patients with NF1-related PN in routine clinical practice. The planned non-interventional PASS will address gaps in knowledge identified by the RMP, including the important identified risk and some of the potential risks and missing information on long-term developmental toxicity in children, by characterising the safety profile associated with selumetinib use among paediatric patients (age d 8 to \< 18 years old) with a diagnosis of NF1 with symptomatic, inoperable PN. This study is a specific obligation in the context of a conditional marketing authorisation for selumetinib (ie, Category 2 PASS). Study results will contribute to updating the safety profile of selumetinib in a relatively large population of patients with different personal characteristics across multiple health care systems and patterns of real-world clinical practice in European countries and Israel. The study will enrol 2 cohorts: 1. The Base Cohort includes all enrolled patients aged 3 to \< 18 years. 2. The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 to \< 18 years who have not reached Tanner Stage V on the index date.

Prevalence, Clinical Characteristics, Progression, and Management of Neurofibromatosis Type 1 in Egypt (NF1-Egy)

Neurofibromatosis type 1 (NF1), a genetic disorder, results from NF1 gene mutations with nearly complete penetrance (1). NF1 is considered common as a rare disease; it has a birth incidence of approximately one every 3000 and a prevalence of one case every 3000-6000 individuals. Patients with NF1 present lifelong phenotypic variabilities, including those mentioned in the National Institutes of Health (NIH) diagnostic criteria: multiple cafe-au-lait macules, freckling, Lisch nodules, cutaneous neurofibromas, plexiform neurofibromas (PNs), optic pathway gliomas (OPG), and osseous lesions (1). Regarding PNs, they are present in about 30-50% of NF1 patients with deeper growth along internal nerve plexus cranial or large peripheral nerve sheaths, compared to cutaneous neurofibromas. NF1 clinical expression is unpredictable, age-related, and varies among patients; additionally, as a tumor predisposition disorder, it is associated with neoplastic complications that impair health-related quality of life (QoL). Thus, it is essential to gather data about the natural history of the disease to understand its burden on patients with NF1 and those who develop PN. Besides that, NF1 prevalence and patients' clinical characteristics are not well recognized in Egypt, and full surgical resection of PN is often challenging due to its invasive nature, location, and size. Accordingly, this is a disease registry to collect data about patients with NF1, both pediatrics and adults. And to understand the natural history of this disorder in Egypt over the past 14 years in real-world settings. For patients with NF1, with or without PNs, we aim to understand their treatment patterns and explore clinical and nonclinical factors influencing targeted outcomes.

Phase I Study to Assess the Effect of Food on the PK and Gastrointestinal Tolerability of Selumetinib in Adolescent Children With Neurofibromatosis Type 1 Related Plexiform Neurofibromas

This study in adolescent participants with NF1 who have inoperable PN is designed to evaluate the effect of a low fat meal on steady state selumetinib exposure; to assess the effect on GI tolerability when selumetinib is dosed under fed and fasted conditions; and potentially, to confirm an appropriate dosing recommendation of selumetinib with a low fat meal that maintains efficacy with acceptable safety. These results may support labelling statements with regard to posology and food.

FARD (RaDiCo Cohort) (RaDiCo-FARD)

The goal of this observational study is to conduct a prospective assessment of the individual Burden of 9 rare skin diseases to assess disability in the broadest sense of the term (psychological, social, economic and physical) for patients and/or families. Two types of indicators will be used to reach this objective : 1. an individual burden score calculated based on a burden questionnaire created specifically, approved and designed to understand the tendency to changes in care and lifestyles. The burden questionnaire should be used by patients and/or their family themselves in self-assessment. 2. a descriptive analysis of all resources (medical and non-medical) used by the family unit to manage the disease.

Familial Investigations of Childhood Cancer Predisposition

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

Neurofibromatosis Type 1 Tumor Early Detection Study

The goal of this observational study is to determine if a liquid biopsy (i.e. blood test) is an effective clinical tool for monitoring the development of malignant peripheral nerve sheath tumor (MPNST) among adults (18 years and older) with Neurofibromatosis Type 1 (NF1), compared to the current standard of care. The main questions it aims to answer are: How effective is liquid biopsy compared to the current standard of care (clinical surveillance and imaging) for early detection of MPNST development among people with NF1? Can liquid biopsy offer a cost-effective method for early detection of MPNST in people with NF1? Also, can liquid biopsy provide earlier detection that potentially leads to better outcomes? Also, can offering liquid biopsy improve access to care for people experiencing barriers to access (such as minority populations or people in rural areas)? At baseline, participants will be asked to: * Complete surveys to provide their demographic and NF1-related health information. * Report whether or not they are experiencing MPNST-related symptoms. * Provide blood samples (15 mL blood total between three tubes, which is approximately one tablespoon). Every six months during the five-year follow-up period, participants will be asked to: * Complete additional surveys to report whether or not they are experiencing MPNST-related symptoms and/or if they have been diagnosed with a new MPNST. * Provide an additional blood sample (10 mL blood total in one tube). If diagnosed with an MPNST by their healthcare provider during the follow-up period, participants will be asked to: * Complete an additional survey regarding their diagnosis and symptoms. * Provide an additional blood sample (10 mL blood in one tube). * In parallel, the study team will request a sample of tumor tissue from the care provider, if available.

Pharmacokinetics, Safety and Efficacy of the Selumetinib Granule Formulation in Children Aged ≥1 to <7 Years With NF1-related Symptomatic, Inoperable PN

This study is designed to define a dosing regimen and assess the pharmacokinetics(PK) and safety of the granule formulation; the study will also include descriptive analyses of exploratory efficacy endpoints. The study will inform the benefit risk profile of the granule formulation in children aged ≥ 1 to \< 7 years with NF1 related symptomatic, inoperable PN.

Natural History Study of Cutaneous Neurofibromas in People With NF1

People diagnosed with NF1 may develop cutaneous neurofibromas, also known as cNFs. These benign tumors can cause discomfort and affect a person's quality of life. Researchers at Johns Hopkins are studying how cNF tumors form, grow and change over time. This information may help doctors in the future, provide early interventions and improve quality of life for NF1 patients. Researchers will also explore a new way of monitoring cNF with 3D camera technology. People of all ages with NF1, living in the United States, are invited to participate in this important research study.

Identification of Pre-Malignant Lesions In Pediatric Patients With Neurofibromatosis Type 1 Using Novel Magnetic Resonance Imaging Techniques Paired With Artificial Intelligence

This is a single arm pilot trial of a novel whole-body Magnetic Resonance Imaging paired with artificial intelligence intervention, to evaluate feasibility defined as scan-rescan reliability, and to estimate the positive predictive value of changes in Magnetic Resonance Imaging scans from baseline to 12-month visit using an Artificial Intelligence algorithm, among 15 pediatric patients with neurofibromatosis type 1 at Cedars-Sinai Medical Center.

Developing Biomarkers of Plexiform Tumor Burden in Patients With Neurofibromatosis-Type 1

The purpose of this study is to identify tumor biomarkers in individuals with Neurofibromatosis type 1 (NF1). Biomarkers are signals that the investigator can measure that tell us about a process such as progress of a disease or treatment. Individuals with this diagnosis are at an elevated risk of developing a type of tumor called a plexiform neurofibroma. Currently, detecting the risk factors of these tumors in children is difficult and requires whole body imaging. The NF1 team at Lurie Children's established a way of using blood plasma in mice with neurofibromatosis type 1 to identify biomarkers that might signal the presence of tumors in people with NF1. This study is an effort to create biomarker profiles of patients with NF1 with known tumors. The study team will utilize whole-body MRI and mass spectrometry (a method for identifying unknown compounds and the properties of molecules). The ultimate goal of this study is to better understand the tumor biomarkers in patients with NF1.

Interventions for Reading Disabilities in NF1

Neurofibromatosis Type 1 (NF1) is a common genetic disorder that is associated with a four times greater risk of learning disabilities, including reading disabilities, and a deficiency of neurofibromin - a protein important in a signaling pathway that regulates learning and memory. Our previous work (NS49096) demonstrated that school-age children with NF+RD can respond to standard phonologically-based reading tutoring originally developed to treat reading disability in the general population. Combining our work with that by other researchers suggesting that a medication (Lovastatin) may counteract the effects of the deficient neurofibromin, and possibly ameliorate learning disabilities in NF1, the investigator propose to examine the synergistic effects of medication plus reading tutoring.