Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
MedulloblastomaEpendymoma3 moreBackground: More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors. Objectives: To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread. Eligibility: Adults whose rare CNS tumor has returned. Design: Participants will be screened: Heart and blood tests Physical and neurological exam Hepatitis tests Pregnancy test MRI. They will lay in a machine that takes pictures. Tumor tissue sample. This can be from a previous procedure. At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life. Participants will get nivolumab in a vein every 2 weeks for up to 64 weeks. Participants will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life. Genetic tests will be done on participants' tumor tissue. Participants will be contacted if any clinically important results are found. After treatment ends, participants will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....
A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
Malignant Glioma of BrainAstrocytoma12 moreThis research study is evaluating an investigational drug, an oncolytic virus called rQNestin34.5v.2. This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug as a possible treatment for this diagnosis of recurrent or progressive brain tumor.
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS...
Malignant Solid NeoplasmRecurrent Adrenal Gland Pheochromocytoma39 moreThis phase II pediatric MATCH trial studies how well tipifarnib works in treating patients with solid tumors that have recurred or spread to other places in the body (advanced), lymphoma, or histiocytic disorders, that have a genetic alteration in the gene HRAS. Tipifarnib may block the growth of cancer cells that have specific genetic changes in a gene called HRAS and may reduce tumor size.
ONC206 for Treatment of Newly Diagnosed, or Recurrent Diffuse Midline Gliomas, and Other Recurrent...
Diffuse Midline Glioma (DMG)Glioblastoma6 moreThis phase I trial studies the effects and best dose of ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors. ONC206 is a recently discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called "stress response" in tumor cells. This stress response causes cancer cells to die, but without affecting normal cells. ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors.
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT
Medulloblastoma RecurrentEpendymoma Recurrent1 morePatients with relapsed medulloblastoma, ependymoma and ATRT have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. Antiangiogenetic therapy has emerged as new treatment option in solid malignancies. The frequent, metronomic schedule targets both proliferating tumor cells and endothelial cells, and minimizes toxicity. In this study the investigators will evaluate the use of biweekly intravenous bevacizumab in combination with five oral drugs (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma and ATRT, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. The primary objective of the MEMMAT trial is to evaluate the activity of this multidrug antiangiogenic approach in these heavily pretreated children and young adults. Additionally, progression-free survival (PFS), overall survival (OS), as well as feasibility and toxicity will be examined.
Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
Neurofibromatosis 2Vestibular Schwannoma3 moreIn this research study the researchers want to learn more about the effects (both good and bad) the study drug selumetinib has on participants with neurofibromatosis type II (NF2) related tumor. The researchers are asking patients with NF2 related tumors to be in the study, because their hearing has decreased and/or their NF2 related tumor has started to grow. The goals of this study are: Determine if selumetinib will stop NF2 related tumors from growing Measure the changes in hearing after receiving selumetinib for 6 months. Determine if selumetinib improves how participants feel (physically and emotionally) and how participants can perform daily activities. Examine tumor tissue, if available, in a laboratory to see if NF2 related tumors have targets of selumetinib.
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma,...
Advanced Malignant Solid NeoplasmMalignant Solid Neoplasm31 moreThis phase II Pediatric MATCH trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back (recurrent) or does not respond to treatment (refractory) and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric...
Central Nervous System TumorPediatric8 moreThis is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4 and CD8 T cells lentivirally transduced to express a HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and young adults with recurrent or refractory HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient meets all other eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meets none of the exclusion criteria, then they can be apheresed, meaning T cells will be collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells. The patient's newly engineered T cells will then be administered via the indwelling CNS catheter for two courses. In the first course they will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Following the two courses, patient's will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available. The hypothesis is that an adequate amount of HER2-specific CAR T cells can be manufactured to complete two courses of treatment with three doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be administered through an indwelling CNS catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study safely can be delivered directly into the brain via indwelling catheter. Secondary aims of the study will include to evaluate CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple time points are available, also evaluate the degree of HER2 expression at diagnosis versus at recurrence.
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With...
Hematopoietic and Lymphoid System NeoplasmRecurrent Ependymoma36 moreThis phase II pediatric MATCH treatment trial studies how well selpercatinib works in treating patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations. Selpercatinib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway (called the RET pathway) and may reduce tumor size.
Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse...
Central Nervous System TumorDiffuse Intrinsic Pontine Glioma11 moreThis is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors. A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meeting none of the exclusion criteria, will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available. The hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.