Clinical Research Directory

Trial Evaluating an Enhanced Physical Activity Intervention to Improve Cognitive Late Effects in Children Treated With Cranial Radiation for Brain Tumors

Background: \- More children with cancer are surviving into adulthood. Some side effects from treatment go away quickly. But some problems may not go away or may only show up months or years later. These problems are called late effects. Late effects can cause difficulties in cognitive functions, such as attention and memory. Physical activity has been found to improve the attention and memory skills of children with Attention Deficit Hyperactivity Disorder (ADHD). Researchers want to see if physical activity can help with these cognitive problems in children with brain tumors. Objectives: \- To see if physical activity can improve cognitive functions in children who had radiation therapy for a brain tumor. Eligibility: \- Children ages 8 17 who had radiation for a brain tumor at least 2 years ago. They must have access to a computer. Design: * Participants will be screened with height, weight, and medical history. They will answer questions about daily physical activities. Their heart will be checked. * Participants will go to the clinic for 2 days. They will have a fitness exam and tests about attention, memory, and concentration. They will have blood taken and answer questions. Parents will also answer questions. * Participants will be put into 2 groups. For the first 12 weeks, the intervention group will follow a physical activity program. The control group will do their usual physical activities. * For the second 12 weeks, the control group will follow the physical activity program. The intervention group will continue the activities on their own. All groups will track their physical activity with an activity monitor and computer. * Participants will have a follow-up visit at the clinic after each session. They will repeat some of the tests listed above. * The study lasts 24 weeks plus the two follow-up visits. Participants can keep their activity monitor.

Observational Trial of the Impact of Radiation Dose in Children With Brain and Skull Base Tumors.

This is a prospective, observational clinical trial investigating the morphological and volumetric changes in the brain following cranial Radiation Therapy in pediatric patients with brain or skull base tumors.

Mapping of Human Cognition

The purpose of this study is to compare organization of normal brain function as detected using Functional magnetic resonance imaging (fMRI) in normal subjects as opposed to patients with epilepsy or brain tumors, to ascribe precise anatomic labels (including Brodmann Areas) and functional significance to each region involved in cognitive processes as detected by cortical stimulation mapping (CSM) in patients with implanted subdural electrodes (SDE) or depth (sEEG) electrodes, to describe the locations of these regions in Talairach space, for a population of patients without overt structural abnormalities in these regions, to generate a spatial probability map of locations of cortical regions "essential" for these processes, to compare the loci of "crucial" language, visual, motor and cognitive sites as determined by CSM with the loci determined by a battery of tasks using fMRI for each individual and to use these data in patients undergoing intracranial electro-corticographyto determine the loci of essential, involved and uninvolved brain areas, and use sophisticated mathematical analyses of these intracranial recordings to study information flow between these areas.

Abemaciclib (LY2835219) in Patients With Recurrent Primary Brain Tumors

The purpose of this study is to test any good and bad effects of a study drug called abemaciclib (LY2835219) in patients with recurrent brain tumors.

Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).

This study will evaluate BCB-276, an investigational B7-H3-targeted Chimeric Antigen Receptor (CAR) T cell therapy, in children and young adults with diffuse intrinsic pontine glioma (DIPG). DIPG is a rare and aggressive brain tumor with limited treatment options. CAR T cell therapy uses a patient's own immune cells that are changed in a laboratory to recognize and attack cancer cells. The purpose of this study is to determine whether BCB-276, when given after completion of standard radiation therapy, is safe and can improve survival for patients with DIPG. To participate, individuals must be between 1 and 26 years of age when they join the study, have a diagnosis of DIPG, and enroll for treatment within 6 weeks of completing initial radiation therapy. Participants must not have received prior anti-cancer therapy beyond radiation with or without temozolomide prior to joining this study. BCB-276 is administered intraventricularly (into the fluid around the brain), which requires placement of a catheter for treatment. BCB-276 is given every 2 weeks at a research center over a period of several months (approximately 7-8 months). Participation includes travel to a study site, procedures to support treatment administration, sample collection, and ongoing monitoring for safety and effectiveness, with follow-up visits lasting up to about 2 years.

Understanding the Late Effects of Surviving a Pediatric Brain Tumor

The goal of this study is to learn about the cognitive and behavioral functioning of children being treated for cancer.

A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main question it aims to answer is: Does niraparib improve overall survival (OS) compared to TMZ? Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ. * study drug (Niraparib) or * comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma). The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks. Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study. Participants' tasks will include: * Complete study visits as scheduled * Complete a diary to record study medication

Asciminib With or Without Sildenafil for Brain Tumors

Dissemination of medulloblastoma is an independent risk factor of poor prognosis. Dissemination of medulloblastoma at recurrence is nearly universally fatal. ABL1 and 2 have been recently found to mediate the dissemination of medulloblastoma. Genetically inactivating ABL1 and 2 resulted in decreased leptomeningeal medulloblastoma and improved overall survival (OS) in rodent models. ABL kinases have also been shown to play a role in the malignant properties of glioblastoma. Asciminib is an FDA approved for the treatment of chronic myeloid leukemia and is well tolerated, likely due to its specificity for ABL1 and ABL2. Asciminib is a P-glycoprotein (P-gp) substrate and thus may be susceptible to being pumped out of tumor cells and brain endothelial cells. It is unclear if asciminib can enter the central nervous system (CNS) and brain tumors in adequate concentration to have anti-tumor effects.

Magnetic Resonance Fingerprinting Guided Extended Resection in Glioblastomas

Magnetic resonance imaging, MRI, is a procedure that uses radio waves, a powerful magnet, and a computer to make a series of detailed pictures of areas inside the body. The goal of this study is to determine if MR fingerprinting, new way of acquiring MRI images, can help identify the extent of tumor spread in the brain, better than routine MRI images.

Panitumumab-IRDye800 to Detect Pediatric Neoplasms During Neurosurgical Procedures

The objective of the study is to assess safety of panitumumab-IRDye800 in pediatric patients undergoing brain surgery to remove suspected tumors.

FIH Clinical Investigation of Graphene Electrodes for Brain Mapping

The goal of this clinical investigation of a medical device is to test the safety of graphene based electrodes when used during surgery for resection of brain tumors. The main questions that it aims to answer are: * To understand the safety of the Graphene Cortical Interface when used during brain tumor surgery (primary objective); * To assess the quality of the brain signals recorded with the Graphene Cortical Interface, their ability to stimulate the brain, how stable their function is over the duration of an operation, and their suitability for use in the operating theatre (secondary objectives). Participants will undergo tumor surgery as usual with the study electrodes being tested alongside a standard monitoring system. If they are awake for part of their surgery they may be asked to complete specific tasks such as naming objects from a list modified for the study, to evaluate the capability to decode brain signals (exploratory objective). They will be monitored subsequently for any complications including undergoing an additional MRI scan 6 weeks after their surgery.

Safety and Effectiveness Evaluation of Temozolomide (Amitzo, NanoAlvand) in Patients With Grade III and IV Glioma Tumors

This is a phase IV, post-marketing, observational, cohort study for safety and effectiveness evaluation of Amitzo® in Iranian patients with grade III and IV glioma tumors. No control group is considered in the study design. The primary objective is to evaluate the incidence of hepatic injury in patients with grade III and IV glioma tumors, treated with Amitzo®.

Cognitive Outcomes After Brain Substructure-informed Radiation Planning in Pediatric Patients

The goal of this trial is to determine whether it is possible to minimize radiation dose to parts of the brain that are important for thinking and learning in children who require radiation to treat their tumor, and if this will help reduce neurocognitive (thinking and learning) impairments in these patients. Patients with newly diagnosed brain or head and neck tumors who are having radiation therapy will have neurocognitive testing and MRI imaging (both research and for regular care) done as part of their participation in the study. Survivors of childhood brain tumors who completed radiation therapy at least two years before joining the study, and have not had a recurrence, will have neurocognitive testing and research MRIs completed. Healthy children will also be enrolled and have research MRIs done. The researchers will use the radiation plan to determine how much radiation was delivered to different parts of the brain. The investigators will use the MRIs to determine how the normal brain is changing after treatment; and how this compares to patients who had standard radiation treatment or who never had a brain tumor. The neurocognitive testing will be compared among different groups to see how different treatment plans affect performance on neurocognitive tests.

A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations

Background: Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed. Objective: To see if a study drug (zotiraciclib) is effective in people with recurrent diffuse gliomas who have IDH1 or IDH2 mutations. Eligibility: People aged 15 years and older with diffuse gliomas that returned after treatment. They must also have mutations in the IDH1 or IDH2 genes. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have an MRI of their brain. A new biopsy may be needed if previous results are not available. Zotiraciclib is a capsule taken by mouth with a glass of water. Participants will take the drug at home on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. They may also be given medications to prevent side effects of the study drug. The schedule for taking the study drug may vary for participants who will undergo surgery. Participants will be given a medication diary for each cycle. They will write down the date and time of each dose of the study drug. Participants will visit the clinic about once a month. They will have a physical exam, blood tests, and tests to evaluate their heart function. An MRI of the brain will be repeated every 8 weeks. Participants may remain in the study for up to 18 cycles (1.5 years).

A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas

The purpose of this study is to evaluate whether treating glioblastoma patients with sitagliptin can improve immune response against the tumor by targeting specific immune cells called myeloid-derived suppressor cells (MDSCs) that suppress your body's natural immune response against cancer. Sitagliptin is an investigational drug for this condition that works by inhibiting an enzyme called dipeptidyl peptidase 4 (DPP-4), which MDSCs rely on to enter the brain and function. While sitagliptin is FDA-approved for diabetes treatment, its use in glioblastoma is investigational (experimental).

Natural History of and Specimen Banking for People With Tumors of the Central Nervous System

Background: Brain and spinal cord tumors are uncommon. But they contribute substantially to cancer deaths in the U.S. in children and adults. Little progress has been made in treating brain tumors. Researchers want to learn more about these tumors by studying people who have them. Objectives: To understand brain and spinal cord tumors better and uncover areas for further research. Also, to connect people with these tumors to doctors who can help them manage their illness and give them new treatment options. Design: Participants will have an initial (baseline) visit. They will have their medical history taken and undergo physical and neurological exams. They will have blood tests. They may have scans (imaging studies) of the nervous system. If participants have urine or cerebrospinal fluid collected during their regular care, researchers may save some. Brain tumor tissue from a prior surgery may be studied. Genomic DNA testing will be done on samples. Results will be linked to participants medical and/or family history. The number of study visits at NIH will depend on the wishes of participants and their local doctors. Participants will take a brain tumor survey on a computer. They can take it all at once or in 6 separate sections. Participants will answer questions about their general well-being. They will answer questions to learn if they have symptoms of depression or anxiety. Physicians will discuss test results with participants. They will recommend management and treatment options.

Functional Organization of the Superior Temporal Gyrus for Speech Perception

The basic mechanisms underlying comprehension of spoken language are still largely unknown. Over the past decade, the study team has gained new insights to how the human brain extracts the most fundamental linguistic elements (consonants and vowels) from a complex and highly variable acoustic signal. However, the next set of questions await pertaining to the sequencing of those auditory elements and how they are integrated with other features, such as, the amplitude envelope of speech. Further investigation of the cortical representation of speech sounds can likely shed light on these fundamental questions. Previous research has implicated the superior temporal cortex in the processing of speech sounds, but little is known about how these sounds are linked together into the perceptual experience of words and continuous speech. The overall goal is to determine how the brain extracts linguistic elements from a complex acoustic speech signal towards better understanding and remediating human language disorders.

Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.

Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases

The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

A Longitudinal Assessment of Frailty in Young Adult Survivors of Childhood Cancer

Advances in cancer therapies have led to increasing numbers of adult survivors of pediatric malignancy. Unfortunately, treatment of childhood cancer continues to require agents designed to destroy malignant cell lines, and normal tissue is not always spared. While early treatment- related organ specific toxicities are not always apparent, many childhood cancer survivors report symptoms that interfere with daily life, including exercise induced shortness of breath, fatigue and reduced capacity to participate in physical activity. These symptoms may be a hallmark of premature aging, or frailty. Frailty is a phenotype most commonly described in older adults; it indicates persons who are highly vulnerable to adverse health outcomes. Frailty may help explain why nearly two thirds of childhood cancer survivors have at least one severe chronic health condition 30 years from diagnosis, why childhood cancer survivors are more likely than peers to be hospitalized for non-obstetrical reasons, and why they have mortality rates more than eight times higher than age-and-gender matched members of the general population. Frailty is a valuable construct because it can be distinguished from disability and co-morbidity, and is designed to capture pre-clinical states of physiologic vulnerability that identify individuals most at risk for adverse health outcomes. These investigators have recently presented data indicating that impaired fitness is present in survivors of childhood acute lymphoblastic leukemia, brain tumor and Hodgkin lymphoma. This is relevant because frailty, characterized by a cluster of five measurements of physical fitness, is predictive of chronic disease onset, frequent hospitalization, and eventually mortality in both the elderly and in persons with chronic conditions. Using a frailty phenotype as an early predictor of later chronic disease onset will allow identification of childhood and adolescent cancer survivors at greatest risk for adverse health. An early indicator of those at risk for adverse health will allow researchers to test, and clinicians to provide, specific interventions designed to remediate functional loss, and prevent or delay onset of chronic health conditions. The investigators goals include characterizing physical frailty over a five year time span in a population of young adult survivors of childhood cancer, as well as assessing the association between frailty and the increase in the number and severity of chronic health conditions.

Cognitive Training in the Virtual Reality Setting With Children Undergoing Radiotherapy for Brain Tumors

The objective of this study is to estimate the feasibility and acceptability of cognitive training in the virtual reality setting with children undergoing radiotherapy for brain tumors. To achieve this goal, the investigators plan to study children undergoing radiotherapy for brain tumors randomly assigned to cognitive training administered via an iPad or virtual reality. Both groups will also participate in cognitive testing and exams using functional near infrared spectroscopy (fNIRS) pre- and post-intervention. The questions to be investigated are: 1. Will cognitive training via virtual reality be feasible and acceptable for children undergoing radiotherapy for brain tumors as indicated by participation rates, adherence and frequency of side effects? 2. Will cognitive training via virtual reality provide neurocognitive benefits? 3. Will there be predictable changes in brain activity as measured by neuroimaging? Findings from this study will be used to develop a larger, definitive trial with direct potential to improve cognitive outcomes for children treated for cancer using a safe and effective alternative to desktop- or laptop-based computerized cognitive interventions with great promise for improving quality of life.

Home-based Vision Rehabilitation Guided by Brain Imaging

The BRIGHT (Behavioral Rehabilitation Through Image-Guided Home-based Training) study aims to evaluate the effectiveness of image-guided, home-based perceptual training at improving visual performance in individuals with visual field loss. Using a prospective, crossover design, BRIGHT combines visual behavioral testing, neuroimaging, and a home-based intervention. It aims to 1) identify neural pathways that support training-induced visual plasticity; and 2) compare the efficacy of different types of visual training delivered in a home-based setting.

CONVIVO Endomicroscopy

Visualization of the tissue microstructure during neurosurgery using a non destructive handheld imaging technology producing a real time digital image ("optical biopsy") at cellular resolution is a novel method that holds great promise for optimization and improvement of the surgical treatment of brain pathologies, brain tumors in particular. The goal of this project is to investigate and assess the ease of use of the CONVIVO FDA cleared system in discriminating healthy and abnormal tissues during in vivo use on the brain during neurosurgery in 30 patients with a working diagnosis of intrinsic brain tumors.

Tolerability and Activity of Brivaracetam (BRV) in Patients With Diffuse Gliomas

The purpose of this study is to determine whether the study medication, brivaracetam, is tolerable and safe for patients with brain tumors.