View clinical trials related to Primitive Neuroectodermal Tumor.
Filter by:This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells that are lentivirally transduced to express an EGFR806 specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor cavity or the ventricular system in children and young adults with recurrent or refractory EGFR-positive CNS tumors. The primary objectives of this protocol are to evaluate the feasibility, safety, and tolerability of CNS-delivered fractionated CAR T cell infusions employing intra-patient dose escalation. Subjects with supratentorial tumors will receive sequential EGFR806-specific CAR T cells delivered into the tumor resection cavity, subjects with infratentorial tumors will receive sequential CAR T cells delivered into the fourth ventricle, and subjects with leptomeningeal disease will receive sequential CAR T cells delivered into the lateral ventricle. The secondary objectives are to assess CAR T cell distribution within the cerebrospinal fluid (CSF), the extent to which CAR T cells egress into the peripheral circulation, and EGFR expression at recurrence of initially EGFR-positive tumors. Additionally, tumor response will be evaluated by magnetic resonance imaging (MRI) and CSF cytology. The exploratory objectives are to analyze CSF specimens for biomarkers of anti-tumor CAR T cell presence and functional activity.
This 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.
Approximately 90% of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease. Despite this terrible and frustrating outcome, continued treatment of this population remains fundamental to improving cure rates. Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances. Moreover, improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all. Novel therapy and, more importantly, novel approaches are sorely needed. This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases. The investigators hypothesize that the use of two predictably active drugs (a doublet) will increase the chance of clinical efficacy. The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy. In addition, a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy. In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased. Furthermore, the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers. PRIMARY OBJECTIVES: - To determine the safety and tolerability and estimate the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of combination treatment by stratum. - To characterize the pharmacokinetics of combination treatment by stratum. SECONDARY OBJECTIVE: - To estimate the rate and duration of objective response and progression free survival (PFS) by stratum.
This phase I/II trial studies the side effects and best dose of melphalan when given together with carboplatin, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive) or has come back (recurrent). Drugs used in chemotherapy, such as melphalan and carboplatin, 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. Osmotic blood-brain barrier disruption (BBBD) uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Sodium thiosulfate may help lessen or prevent hearing loss and toxicities in patients undergoing chemotherapy with carboplatin and BBBD. Giving melphalan together with carboplatin, mannitol, and sodium thiosulfate may be an effective treatment for recurrent or progressive CNS embryonal or germ cell tumors.