View clinical trials related to Pleomorphic Xanthoastrocytoma.
Filter by:Pediatric low-grade glioma (PLGG) is a heterogeneous group of WHO grade I and II brain tumors, associated with a 10-year overall survival of 90%. It is the most common form of primary central nervous system (CNS) tumor arising during childhood, adolescence and young adulthood, accounting for over 30% of CNS tumors in this age group. A large group of PLGG patients will benefit from a complete resection of their tumor. Nevertheless, PLGG can occur anywhere and can be in some locations associated with neurological symptoms, unresectable or radiological progressive tumors that need medical treatments rapidly to avoid long-term sequelae. The current problem during this first line therapy is to improve tumor response, overall survival rate, as well as progression free survival. In our study, we will focus on a specific group of PLGGs without any congenital NF1 mutation and with a wild-type BRAF gene in the tumor. In this subgroup, for instance, the PFS is not increasing anymore above 50% at 3 years independently from the chemotherapeutic scheme. The two current standard therapies are carboplatin plus vincristine during 81 weeks or a weekly IV administration of vinblastine during 70 weeks. The most recent Canadian approach with vinblastine seems to have the same PFS rate, but with a better daily tolerance and less toxicities than the carboplatin/vincristine combination. Therefore, it is becoming the new standard approach in those patients. Nevertheless, we need to improve more their outcome with less recurs and a better first-line tumor response. The recent molecular discoveries involving the Ras/mitogen-activated protein kinase pathway in those PLGG is opening a new era with specific targeted therapies that might be the key to improve their survivals and giving hope to less treatment lines and a better tumor response. Therefore, we designed a prospective open randomized phase II study, named PLGG-MEKTRIC, comparing the experimental arm (a daily MEK inhibitor, Trametinib, Mekinist©) to a standard arm comprising weekly vinblastine during 18 courses of 4 weeks each. The study will enroll 134 patients with a PLGG during childhood, adolescence or young adulthood with no NF1-related disease and without any BRAFv600 mutation located in brain or spine. 67 patients, in each treatment arm, are planned to be enrolled to answer our primary objective. This primary objective will be to determine in the experimental arm a 20% superiority of the 3-year PFS rate in comparison with the standard treatment administered during 18 courses (e.g. 72 weeks). A stratification of the patients will be done in both arms based on molecular tumor results and brain/spine locations to obtain two equivalent arms to be analyzed. The recruitment time will be 36 months and the complete follow-up of each patient will last 3 years. The secondary objectives will be in both arms: the tumor response rate at 24 and 72 weeks of treatment, the 3-year PFS and OS rates and the frequency of AE/SAE/SUSAR (Adverse Event/Serious Adverse Event) based on CTCAE criteria during the 3 years after the first administration. A Quality of Life (QoL) assessment, based on PEDsQL questionnaires, at 24 weeks, at the end of treatment and 3 years after 1st treatment administration in both arms will be part of this study. Finally, 3-year PFS and OS will be analyzed according to molecular biomarkers and visual assessment (LogMar scale) in each arm. An economic analysis is also planned as an ancillary study to determine a cost effectiveness of the best arm and complementary ancillary molecular studies are already organized. In the future, we hope to push forward this new-targeted therapy as a referenced first line treatment of pediatric PLGG to obtain the best tolerance and positive long-term impact and to extend our knowledge of MEK inhibitor impact in molecular subgroups and in optical pathway locations. We also plan to do a "switch" strategy in patients relapsing in standard arm and we will propose systematically to those patients the experimental treatment (MEK inhibitor ).
The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms.
Low-grade gliomas (LGGs) are the most common brain tumors in children, and a subset of these tumors are treated definitively with focal radiation therapy (RT). These patients often survive for many years after receiving RT and experience late deficits in memory. Verbal recall is an important measure of memory and is associated with other important functional outcomes, such as problem-solving, independence of every-day functioning, and quality of life. Decline in memory, as measured by verbal recall, is associated with RT dose to the hippocampi. Therefore, this phase II study investigates the feasibility of reducing RT doses to the hippocampi (i.e., hippocampal avoidance [HA]) by using proton therapy for midline or suprasellar LGGs. Primary Objective: - To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs. Feasibility will be established if 70% of plans meet the first or second dose constraints shown below. 1. First priority RT dose constraints for bilateral hippocampi: volume receiving 40 CGE (V40CGE) ≤ 25%, dose to 100% of Hippocampus (D100%) ≤ 5CGE. 2. Second priority RT dose constraints for bilateral hippocampi: V40CGE ≤ 35%, D100% ≤ 10 CGE. Secondary Objectives: - To estimate the 3-year event-free-survival (EFS) for LGGs treated with HA. - To estimate the change in California Verbal Learning Test short-term delay (CVLT-SD) from baseline to 3 years and from baseline to 5 years - To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that: (1) meet first priority RT dose constraints, (2) meet second priority RT dose constraints but not first priority RT dose constraints, and (3) that did not meet either first or second RT priority dose constraints Exploratory Objectives: - To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery, including gold standard measures shown in the published studies to be sensitive to attention, memory processing speed and executive function that will afford comparison to historical controls. - To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi. - To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography (MET-PET) uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology. - To investigate the effect of BRAF alteration, tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner. - To investigate whether the methylation profiles of LGGs differ by tumor location (thalamic/midbrain vs. hypothalamic/optic pathway vs. others) and histologies (pilocytic astrocytoma vs. diffuse astrocytoma vs. others), which, in conjunction with specific genetic alterations, may stratify patients into different subgroups and highlight different therapeutic targets. - To record longitudinal measures of circulating tumor DNA (ctDNA) in plasma and correlate these measures with radiographic evidence of disease progression. - To bank formalin-fixed, paraffin-embedded (FFPE)/frozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol. - To quantify and characterize tumor infiltrating lymphocytes (TILs) and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment. - To estimate the cumulative incidence of endocrine deficiencies, vision loss, hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy.
A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.
This is a study to determine the safety and efficacy of the drug, mebendazole, when used in combination with standard chemotherapy drugs for the treatment of pediatric brain tumors. Mebendazole is a drug used to treat infections with intestinal parasites and has a long track record of safety in humans. Recently, it was discovered that mebendazole may be effective in treating cancer as well, in particular brain tumors. Studies using both cell cultures and mouse models demonstrated that mebendazole was effective in decreasing the growth of brain tumor cells. This study focuses on the treatment of a category of brain tumors called gliomas. Low-grade gliomas are tumors arising from the glial cells of the central nervous system and are characterized by slower, less aggressive growth than that of high-grade gliomas. Some low-grade gliomas have a more aggressive biology and an increased likelihood of resistance or recurrence. Low-grade gliomas are often able to be treated by observation alone if they receive a total surgical resection. However, tumors which are only partially resected and continue to grow or cause symptoms, or those which recur following total resection require additional treatment, such as chemotherapy. Due to their more aggressive nature, pilomyxoid astrocytomas, even when totally resected, will often be treated with chemotherapy. The current first-line treatment at our institution for these low-grade gliomas involves a three-drug chemotherapy regimen of vincristine, carboplatin, and temozolomide. However, based on our data from our own historical controls, over 50% of patients with pilomyxoid astrocytomas will continue to have disease progression while on this treatment. We believe that mebendazole in combination with vincristine, carboplatin, and temozolomide may provide an additional therapeutic benefit with increased progression-free and overall survival for low-grade glioma patients, particularly for those with pilomyxoid astrocytomas. High grade gliomas are more aggressive tumors with poor prognoses. The standard therapy is radiation therapy. A variety of adjuvant chemotherapeutic combinations have been used, but with disappointing results. For high-grade gliomas this study will add mebendazole to the established combination of bevacizumab and irinotecan to determine this combinations safety and efficacy