Active clinical trials for "Neurofibromatoses"

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, which are benign nerve sheath tumors that may cause severe morbidity and possible mortality. The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability. Gene profile analysis demonstrates overexpression of fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor in plexiform neurofibromas in patients with NF1. Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors. Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas. A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed, and has established the phase II dose (the dose resulting in a mean drug exposure [AUC] not more than 1 standard deviation below the mean drug exposure [AUC] in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions). Pirfenidone has been well tolerated. Objectives: To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas. To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas. To describe and define the toxicities of pirfenidone. Eligibility: Individuals (greater than or equal to 3 years to less than or equal to 21 years of age) with a clinical diagnosis of NF1 and inoperable, measurable, and progressive plexiform neurofibromas that have the potential to cause substantial morbidity. Design: The phase II dose will be used in a single stage, single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown. For this reason, time to disease progression on the placebo arm of an ongoing National Cancer Institute (NCI) Pediatric Oncology Branch (POB) placebo-controlled, double-blind, cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas. Funding source - Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD)

It is known that children with NF1 can have weak muscles and suffer from tiredness. It is also known that in similar conditions affecting children's muscles, standing on a vibration device for a few minutes each day can strengthen muscles and improve their ability to perform day-to-day activities. The investigators believe this vibrating platform can be used to strengthen the muscles of children with NF1 also, beyond standard exercises, and therefore allow them to perform day-to-day activities better, do more activity and feel less tired. If families are keen to take part in this study, the investigators will first need to check they are suitable for the trial. This will be based on the participant's age (6-16 years), their other medical problems that would affect use of the vibration device or tests to assess how effective it is, and their level of muscle weakness. Once families have agreed to take part, participants will be randomised either to receive a muscle-strengthening exercise session delivered by a physiotherapist that children with weak muscles should continue to perform daily for the next 6 months; or to receive a vibration device to take home and use for a few minutes 5 days a week for 6 months as well as the exercises. All participants will be invited to attend for a variety of activities and tests, just before starting the trial and 6 months later at the end of the trial to see if there is any benefit from the vibration device. The investigators will repeat these tests again 3 months later, to see if any benefits observed remain, even after the device is removed. They will involve jumping, hopping and balancing on a board, gripping a machine as hard and as long as possible, being fitted with a device that measures activity for 7 days, walking as far as possible for 6 minutes, scanning muscles using MRI, completing a tiredness and general well-being questionnaires, and parents completing a questionnaire of the participant's attention and intellect. The jumping will also be performed 3 months into the study, to see if there is any early improvement in this key test. All participants will be given full details of what the trial involves before taking part. As with any other trial, participants and their families are free to stop taking part at any time. Although the investigators do not anticipate any safety issues, if any do arise, the families will be asked to contact the trial team.

This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 & 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 at 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period.

The main objective of the study is to assess the efficacy of a home-based, computerized cognitive training (CT) program, called CogmedRM, targeted to improve working memory in children with NF1 and working memory difficulties. This is a Phase II randomized parallel group controlled clinical trial comparing two interventions on cognitive outcomes. Participants will be stratified by stimulant medication use and randomized equally between the two interventions within stratum. Participants will be in the study for to 11 weeks.

This clinical trial is conducted by one of 4 locations; University of British Columbia (Vancouver, CA), University of Utah (Salt Lake City, UT, USA), University of Cincinnati (Cincinnati, OH, USA), and University of Hamburg (Hamburg, Germany). Adults with NF1 have a higher risk of osteopenia and osteoporosis, a condition of low bone density that can lead to fragile bones and bone breakage. People with NF1 also have lower vitamin D levels than unaffected individuals. Vitamin D is important for normal bone health, but studies to improve bone health by vitamin D supplementation in people with NF1 have not been tried. The purpose of this study is to treat adults with NF1 who have insufficient serum vitamin D levels with 2 different doses of vitamin D supplementation to determine if vitamin D supplementation ameliorates the usual loss of bone mineral density over 2 years.

This is a second Pilot Study to determine the efficacy of Gleevec® in neurofibromatosis (NF1) patients with plexiform neurofibromas using new response assessment modalities with the secondary goals of assessing Gleevec toxicity, and characterizing markers of response. The rationale for this study arises from the response of human and murine NF1 cells to Gleevec® in vitro, the response of a NF1 patient treated with Gleevec® for airway compression by a plexiform neurofibroma with a dramatic response not previously seen in NF1 therapy, and the experience in 37 NF1 patients treated with Gleevec® in the initial pilot study. Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid. Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.

This is a study to gather some information on the safety and efficacy of the penetrating auditory brainstem implant (PABI) in patients with neurofibromatosis type 2.

This phase I trial studies the side effects and best dose of pomalidomide in treating younger patients with tumors of the brain or spine (central nervous system) that have come back or are continuing to grow. Pomalidomide may interfere with the ability of tumor cells to grow and spread and may also stimulate the immune system to kill tumor cells.

This study, "A Phase II Study of Cabozantinib (XL l84) for Plexiform Neurofibromas in Subjects with Neurofibromatosis Type I in Children and Adults diagnosed with Neurofibromatosis Type 1 (NF1) and have a type of tumor called a plexiform neurofibroma (PN). Neurofibromas are tumors that develop from the cells and tissues that cover the nerves. Plexiform neurofibromas can be disfiguring, painful, and life-threatening. These types of tumors typically do not respond well to most treatment approaches such as chemotherapy, radiation, and surgery because of their slow growth and location near vital structures of the body such as nerves, blood vessels, and the airway. The primary objective is to determine the response rate of NF1 patients with plexiform neurofibromas treated with Cabozantinib therapy using MRI scans. The objective response rate to cabozantinib is defined as ≥ 20% reduction in tumor volume at the end of 12 cycles.

The purpose of this study is to determine if the study drug, AXITINIB, has any effect on tumors found in patients with Neurofibromatosis Type 2 (NF2).