Gliadel

Background: Cognitive symptoms are common and often severe in patients with brain metastases, significantly impacting their quality of life and ability to manage cancer care. Currently, there is no standard approach for routinely assessing and managing these symptoms in oncology clinics. Objective: This study aims to evaluate the feasibility, acceptability, and preliminary efficacy of the Cognitive Stepped Care Program (CSCP) in a Brain Metastases Clinic. Methods: This is a prospective, mixed-methods feasibility study involving patients with brain metastases, their caregivers, and clinic staff. Patients will undergo routine cognitive symptom screening using a standardized tool. Based on symptom severity, they will receive tiered interventions ranging from no support, to education materials, to computerized cognitive testing with individualized debrief, with group strategy training and/or neuropsychological consultation, as needed. Patients will complete questionnaires before and after the intervention regarding their symptoms and quality of life. Patients, caregivers and staff will provide their feedback about the intervention through questionnaires and interviews. Outcomes: Primary outcomes include feasibility and acceptability of the CSCP. Secondary outcomes include preliminary changes in cognitive symptoms, self-efficacy, and quality of life. Significance: This study will inform the potential integration of a structured cognitive support program into standard care for patients with brain metastases and may provide a model for similar interventions in other oncology settings.

The goal of this clinical trial is to first define the Safety and Optimal Biological Dose (OBD) of study drug TGX-007 and to then further investigate the safety and efficacy in patients with newly diagnosed or recurrent Glioblastoma. TGX-007 is a gene therapy drug delivered by a harmless adeno-associated virus (AAV) vector which delivers two combined therapeutic payloads to enable killing of proliferative cells and activation of an anti-tumour immune response. One is herpes simplex virus thymidine kinase (HSV-tk), which converts the pro-drug valaciclovir into an active drug that can kill tumour cells and the other is interleukin 12 (IL-12), which activates the body's immune system to recognise and fight the tumour. Patients newly diagnosed with glioblastoma suitable for standard of care surgery and chemoradiotherapy or patients with recurrent glioblastoma suitable for further surgery may be eligible for the study. Patients will receive TGX-007 by a direct intratumoural injection and will then take the pro-drug valacyclovir orally for up to 21 days before proceeding to standard of care surgery. The study is split into two phases. Phase I will treat patients at different dose levels of TGX-007 to identify the Optimal Biological Dose that will be used to further expand the study into Phase II. Phase II will expand the number of patients treated at the selected OBD to investigate how effective TGX-007 is at treating newly diagnosed and recurrent GBM. Approximately 68 people aged 18-70 will take part in the study.

This is a phase 1 study for patients with newly diagnosed MGMT unmethylated IDH wild-type glioblastoma utilizing autologous activated T-cells armed with bispecific antibody (EGFR-BATs) that recognize the tumor. The investigators hypothesized that the combination of infusions of EGFR BATs and low-intensity focused ultrasound would induce blood-brain barrier opening and increase the permeability of the adoptive immunotherapy. The investigators will radiolabel the EGFR BATs with 89Zr-oxine for subsequent PET imaging to determine the trafficking and uptake of this approach. There is a concern that several infusions of EGFR BATs before BBB opening could change the immune tumor microenvironment that would not allow a permissive BBB after LIFU. Therefore, Arm A will have two LIFU with BBB opening after the 4th and the 8th infusion, and Arm B will have three LIFU with BBB opening after the 1st, 4th, and 8th infusions. This study will determine the safety and feasibility of the combination of low-intensity focused ultrasound (LIFU) with microbubbles BBB opening and EGFR BATs and the access of the adoptive cell immunotherapy to the tumor microenvironment to inform future studies.

This will be an open-label Phase 0/1 study that will enroll approximately 15 participants, 9 participants with recurrent WHO Grade 4 glioma (rGBM) and 6 participants with brain metastases, who will receive the investigational drug risvutatug rezetecan (GSK5764227), a B7-H3-targeted antibody-drug conjugate (ADC) with the GSK5757810 payload. The trial will consist of a Phase 0 component (subdivided into Arms A and B) and an Expansion Phase 1 component. Participants with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component will be eligible to enroll in the Expansion Phase to receive therapeutic dosing of risvutatug rezetecan.

This is a randomized, phase II trial comparing staged stereotactic radiosurgery (SSRS) versus fractionated stereotactic radiotherapy (FSRT) in patients with large brain metastases (≥2 cm and ≤5 cm). The study aims to evaluate efficacy, safety, and tumor response between these two standard-of-care radiation approaches.

CAR-T cell therapy is an emerging treatment modality in relapsed and refractory multiple myeloma (MM). CAR-T therapy in MM relies on directing autologous T-cells to detect and clear myeloma cells expressing B-cell Maturation Antigen (BCMA). While BCMA CAR-T cell-treated patients achieve an excellent overall response rate, their response is often not durable. NT-I7 promotes CAR-T cell expansion and efficacy in pre-clinical lymphoma models. In patients receiving CD19-directed CAR-T therapy for lymphoma, NT-I7 augmented CAR-T expansion while being safe and tolerable. The impact of NT-I7 on BCMA CAR-T cells in multiple myeloma is unknown. This is a two-arm, double blind, placebo-controlled, randomized, single-site phase Ib study testing the safety and toxicity of adding NT-I7 to BCMA CAR-T therapy in patients with relapsed and refractory multiple myeloma. The hypothesis is that NT-I7 will promote CAR-T expansion and persistence which will enhance clearance of MM, while maintaining a favorable safety and toxicity profile. Patients receiving standard of care BCMA CAR-T (Cilta-cel) will be randomized to either NT-I7 or placebo. Correlative studies will evaluate CAR-T cell expansion, persistence, immune-phenotype, function and correlate with clinical outcomes.

The purpose of the study is to determine the recommended dose and further understand the safety of MT-125 in participants who have been diagnosed with glioblastoma, a primary brain tumor, when administered in combination with your standard of care treatment. Initially, participants with newly diagnosed glioblastoma will be given different doses of MT-125 in combination with radiotherapy (RT) with the goal of identifying the highest tolerated dose. Up to 36 people with glioblastoma who are at least18 years old are being invited to join this study. MT-125 is a type of study treatment which acts on cancer cells in the brain to destroy them. It will be administered on the same day as your standard of care radiotherapy because it is also designed to help radiotherapy work better. However, this is the first time MT-125 will be studied in humans. Therefore, the use is considered investigational. If you would like more details about MT-125 in glioblastoma participants, please ask the Study Doctor. You will be among the first participants with glioblastoma to receive this study treatment. Its safety and effectiveness have not yet been established in humans. Thus, we do not know whether it will work for you. Your condition may improve, may get worse, or there may be no change. The selected participant population-individuals newly diagnosed with histologically and/or molecularly confirmed IDH wild-type, MGMT-unmethylated glioblastoma-represents those least likely to experience safety concerns or adverse events related to the study treatment, and most likely to derive therapeutic benefit. There are certain tests/questions you must complete to find out if you meet the requirements to be in the study. If you do not meet these requirements, you cannot take part in the study. If this happens, you can talk to your Study Doctor about other options.

To characterize feasibility, safety, and/or preliminary efficacy of personalized strategies to adapt standard radiotherapy treatments to individual patient responses.

standard paradigm for management of patients who present with concern for recurrence of brain metastases following initial stereotactic radiosurgery (SRS).

Perioperative treatment of newly diagnosed cancer patients with brain metastasis without dexamethasone (Dex).

The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.

This is a single-arm open-label phase 1 dose escalation/expansion trial assessing the safety and efficacy of concurrent intrathecal azacitidine and intrathecal nivolumab in recurrent high-grade glioma.