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This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.
Paclitaxel is among the most active agents against glioblastoma in preclinical models. However, its clinical use has been hampered by the blood-brain barrier (BBB). In this trial we will implant a novel device with 9 ultrasound emitters allowing to temporarily and reversibly open the BBB immediately prior to chemotherapy infusion with albumin-bound paclitaxel. In the phase 1 component, increasing doses of chemotherapy will be delivered as long deemed safe based on the prior patient not experiencing severe toxicity. Once the the recommended dosing has been established, carboplatin will be added to the regimen and additional...
The usual standard of care for patients over 65 diagnosed with glioblastoma ("GBM") or Grade 4 astrocytoma, IDH-mutant is a 3-week course of radiotherapy, with concurrent and adjuvant temozolomide (TMZ). This radiation dose and length of treatment are less than what would be given for younger patients, primarily due to unclear survival benefits from randomized trials. However, survival remains dismal, and may be partially due to the reduced radiation dose. Recent studies investigating this have found that increased radiation dose (to the equivalent of what is normally given over 6 weeks in younger patients) over 3 weeks is ...
The goal of this study is to test whether an adaptive radiation therapy (RT), two-phase approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT approach. The main questions of the study are to see how this adaptive, two-phase RT approach compares to standard RT in terms of: - Local control - Overall and progression-free survival - Patterns of failure - Toxicity, Neurological Function, and Quality of Life
In many patients with an acute unilateral vestibular deafferentiation (uVD) syndrome symptoms are expected to resolve spontaneously because of central compensation. However, more detailed observations have revealed that 29-66 % of uVD patients develop disabling chronic dizziness lasting >1 year after the acute event. Identifying predictors of chronic dizziness would allow patients at high risk to be targeted with personalized therapies to reduce healthcare costs. Therefore, the main objective of this study is to identify predictors of chronic dizziness after an acute uVD. Despite the consensus on the usefulness of physical therapy, ...
The purpose of the study is to understand the extent and degree of somatostatin receptor expression in poorly differentiated neuroendocrine carcinomas . This may help to make a determination if a radiolabeled somatostatin analog therapy, also referred to as peptide receptor radiotherapy (PRRT), can be a potential alternative in the future. At this time, radiolabeled somatostatin analogs have not been tested in patients with poorly differentiated neuroendocrine carcinomas, and their efficacy in this disease is not well known Understanding the extent and degree of somatostatin receptor expression is important in order to evaluate the...
Standard Magnetic Resonance Imaging (MRI) is based on the excitation of hydrogen nuclei that are presents in water molecules, which abundance in human body allows for obtention of superior contrast. However, assessing the presence of other molecules than water in tissues is also of great clinical interest to probe metabolites related to physiological body function and pathological conditions. Chemical exchange saturation transfer (CEST) allow to overcome some limitations of proton magnetic resonance spectroscopy (1H-MRS) by exploiting chemical properties of the targeted molecule through a continuous process of re-saturation and...
Vestibular schwannomas (VS) arise from the vestibulocochlear (hearing and balance) nerve, located at the base of the brain. Although benign, VS can enlarge over time, resulting in debilitating symptoms; therefore, surgical removal is frequently offered. One significant risk of surgery is inadvertent injury to the facial nerve, which lies adjacent to the vestibulocochlear nerve. Currently, the nerve's course is only revealed during surgical dissection and injury can cause permanent facial weakness. It would therefore be useful for the surgeon to know the course of the nerve before operating. To this end, a new MRI technique known as...
The present study aims to investigate the potential application of multispectral analysis, hyperspectral imaging, and fluorescence during neuro-oncological procedures, specifically during brain tumour debulking / resection. These optics techniques are entirely non-invasive and consist in camera with a filter to be linked to the standard microsurgical and endoscopic instruments used in theatre. The research procedure consists of images acquisition and data processing, with virtually no additional invasive procedures to be performed on patients.
Re-irradiation in gliomas is a therapeutic option at recurrence before of 2nd-line chemotherapy. The dose of re-irradiation with conventional fractionation is unfortunately limited by the risk of symptomatic radionecrosis that is significant for cumulative doses above 100 Gy. The use of unconventional low dose rate pulsed radiotherapy (pLDRT) can reduce the risk of radiotoxicity while taking advantage of the cellular hyper-radiosensitivity that occurs at low dose-rates. The present study therefore aims at evaluating whether the use of pLDRT in the re-irradiation of recurrences of gliomas allows maintaining a low risk of symptomatic...
