Temozolomide

Pediatric patients receiving proton therapy for solid tumors or Hodgkin's lymphoma may experience anatomical changes during treatment that can affect proton therapy accuracy. This prospective single-arm study uses regular low-dose imaging to monitor these changes and adjust treatment plans as needed. Participants will receive weekly or every-other-week CT scans, with MRI when appropriate, to assess whether the original plan remains accurate. Treatment plans will be updated if tumor coverage decreases by more than 5% or if radiation dose to normal tissues increases by more than 10%; otherwise, the original plan will continue. The study aims to determine how often plan adjustments are needed and to identify which disease sites are most likely to experience significant anatomical changes during treatment. Primary Objective: * Define the frequency of replanning necessary to ensure tumor coverage never falls below 95% (or 5% drop) of the prescribed daily dose in participants with intact (gross) tumors to keep the tumor control optimal throughout the multi-week treatment regimen. * Define the frequency of replanning necessary to ensure organs-at-risk (critical organs) do not deviate by more than 10% of the initially approved dose constraints to keep the normal tissue complication minimal throughout the multi-week treatment regimen. Secondary Objectives * Establish a cone beam CT (CBCT)-based framework for quantifying body surface changes throughout the treatment course. This goal will be achieved by developing a novel algorithm that detects and tracks external anatomical variations longitudinally, without requiring CBCT image enhancement, enabling precise assessment of daily participant setup consistency and anatomical stability. * Overcome daily CBCT quality limitations by generating synthetic CT images that accurately represent daily anatomy and support proton dose recalculation or verification planning. This goal will be achieved by developing a hybrid pipeline that integrates deep learning models with the deformable image registration algorithm, trained and validated on disease site-specific data. This will enable precise dose mapping and tissue density estimation, directly supporting adaptive planning decisions without the need of diagnostic- quality CT images.

This is an open-label, multi-center, Phase 0/2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067. The study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12). The Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.

This study builds on the results of prior studies (UNITED and UNITED-3). The goal of UNITED-4 is to test whether an adaptive radiation therapy (RT) therapy approach ('dose painting'), with reduced margins, impacts 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 RT approach with reduced margins compares to standard RT in terms of: * Local control * Overall and progression-free survival * Patterns of failure * Toxicity, Neurological Function, and Quality of Life * Longitudinal imaging features

The goal of this study is to build on the experience of the SAINT trial by evaluating the safety and efficacy of the addition of pazopanib to their published chemotherapy regimen.

Background: Glioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells. Objective: To test LMP744 in people with glioblastoma. Eligibility: People aged 18 years or older with glioblastoma that returned after treatment. Design: Participants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function. Participants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a port under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein. LMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time. Participants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery. Participants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits. Participants will continue to have telehealth visits every 3 months after they stop taking the drug.

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.

The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting. Specifically, this study is being done to find answers to the following questions: * How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM? * What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)? * Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?

To learn if zanzalintinib and pembrolizumab can help to control select subtypes of advanced/metastatic soft-tissue sarcoma (UPS, MFS, HGPS, and HGUS

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.

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-DFC413 and safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with solid tumors

The goal of this clinical trial is to compare whether the use of videoconferencing in breast cancer patients undergoing radiotherapy is better for pre-treatment education than telephone calls. The main question it aims to answer is in breast cancer patient receiving radiotherapy, does videoconferencing, compared to telephone calls for pre-treatment education result in decreased procedural fears and concerns? The investigators hypothesize that the use of videoconferencing for pre-treatment radiotherapy education will decrease breast cancer patients' procedural fears and concerns. Researchers will compare the current standard of care in a 30 minute radiation therapist led pre-treatment education call to the intervention of a 45 minute radiation therapist led videoconferencing call to see if the intervention reduces patient procedural fears and concerns, anxiety levels, and has higher patient satisfaction. Participants will be asked to complete questionnaires at three time points: 1. Baseline - at time of study consent. 2. CT-Simulation - after their radiotherapy CT-Simulation appointment. 3. Day 1 Treatment - after their first day of radiotherapy treatment.