Brain Metastases

This is a single-center, open-label, multi-cohort Phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with solid tumors and brain metastases. The study will be comprised of 3 patient cohorts: triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and solid tumor types other than TNBC and NSCLC. Cohort 3 will be comprised of solid tumor types with established (e.g., renal cell carcinoma \[RCC\], endometrial cancer) or preliminary clinical evidence (e.g., gastric cancer, colorectal cancer) of efficacy of programmed cell death-1 (PD-1) and angiogenesis inhibitors. The study will be conducted using a Simon's optimal two-stage design, and approximately 87 patients will be enrolled concurrently (n=29 per cohort). The primary endpoint is intracranial objective response rate (ORR) as assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy. To learn if using SRS to treat all brain metastases that do not respond to systemic therapy versus treating only metastases that are getting worse can help to control CNS disease in patients whose disease gets worse after systemic therapy.

This phase III trial compares the effect of stereotactic radiosurgery and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain.

GENCONCOR-2 is a translational research aimed to compare the molecular profile of primary tumors and their matched brain metastases in gastroesophageal cancers, including cancer of the esophagus, gastroesophageal junction, and stomach. The study is based on the previously established international GASTROBRAIN cohort (ClinicalTrials.gov ID: NCT07448493), which provides comprehensive clinicopathological and treatment data for over 230 patients. It will be conducted by retrospective analysis of paired samples of histological material (primary tumor and corresponding brain metastasis) with determination of HER2 expression status (IHC ± FISH), MSI status (IHC ± PCR), PD-L1 combined positive score (CPS), and CLDN18.2 expression status (IHC)

A phase I clinical trial (a type of research study) for people with human epidermal growth factor receptor 2 (HER-2) positive breast cancer with metastasis to the brain. This research study will evaluate how well brain metastases can be controlled using a type of radiation therapy known as stereotactic radiosurgery (SRS) when combined with the therapeutic agent Trastuzumab Deruxtecan (T-DXd). The combined use of SRS with T-DXd is considered investigational.

This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.

Participants in this research study have cancer that has spread to their brain, called brain metastases. One treatment for this type of cancer is called whole brain radiotherapy that stays away from a specific neurocognitive substructure, called the hippocampus, combined with medication to preserve cognitive function. This study compares that approach to another approach of whole brain radiotherapy that stays away from additional structures that are thought to have a role in cognitive function. Researchers want to see if there is a difference in the preservation of cognitive function between these two approaches.

A Phase II Study of Nivolumab with Ipilimumab and Cabozantinib in Patients with Untreated Renal Cell Carcinoma Brain Metastases

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

The goal of this diagnostic intervention clinical trial is to compare 18F-Fluciclovine uptake within brain lesions over 60 minutes compared with standard of care positive histology confirmation or confirmation MRI images. The main questions it aims to answer are: 1. What are the dynamics of 18F-Fluciclovine update within a non-treated metastatic brain lesion over 60 minutes? 2. What are the dynamics of 18F-fluciclovine update within recently treated metastatic brain lesions? 3. What is the potential use of 18F-Fluciclovine in delineating true local progression from radionecrosis in patients with clinical uncertainty of indeterminate MRI? Participants will undergo an 18F-fluciclovine head PET/CT scan prior to treatment for brain metastatic lesion(s). The study will characterize uptake dynamic PET images over 60 minutes. Uptake within the lesions and the benign brain parenchyma will be plotted on a time activity curve for 60 mins. Patients will undergo a second 18F-fluciclovine PET/CT to evaluate 18F-fluciclovine uptake in treated lesions over 60 minutes. This will be offered concurrently with the post-procedure standard of care (SOC) MRI to evaluate post-treatment changes. Uptake within the lesions and the benign brain parenchyma will be plotted on a 60 min time activity curve. Results will be compared to the pre-treatment baseline images. A third 18F-fluciclovine PET/CT will be offered to evaluate post radiation changes necrosis from recurrence, for up to 10 patients in our cohort who are under clinical surveillance (up to three years surveillance) and developed MRI evidence of either true progression or radionecrosis with clinical uncertainty after stereotactic radiosurgery. The initial 18F-fluciclovine PET/CT will serve as a baseline PET/CT scan. This will be compared to post procedural histological confirmation.

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.

The purpose of this study is to discover the potential convenience and ease of using a Magnetic Resonance Imaging (MRI) technique, named Magnetic Resonance Fingerprinting (or MRF), to achieve high-quality images within a short scan time of 5 min for viewing the entire brain. This is an advanced quantitative assessment of brain tissues. This method is being applied with IVIM MRI to be able to tell the difference between a brain with radiation necrosis and a brain with tumor recurrence. Participants will consist of individuals who have received radiation therapy in the past and were diagnosed with radiation necrosis, individuals with recurrent tumors, individuals with previously untreated tumors, and healthy individuals who have no brain diseases and have not had radiation treatment to the brain. Participants will undergo an MRI scan at a one-time research study visit; no extra tests or procedures will be required for this research study. The primary objectives of this study are: * To demonstrate the clinical feasibility of combining MRF with state-of-the-art parallel imaging techniques to achieve high-resolution quantitative imaging within a reasonable scan time of 5 min for whole brain coverage. * To apply the developed quantitative approach in combination with IVIM MRI for differentiation of tumor recurrence and radiation necrosis. * To investigate the effect of radiation dose on the development of radiation necrosis and tumor recurrence.

BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Highly vascular brain tumors, including meningiomas, hemangioblastomas, and certain metastases, have a rich blood supply that can lead to substantial blood loss and technical difficulties during surgical removal. Preoperative endovascular embolization is an adjunctive, catheter-based procedure used to block the feeding blood vessels of the tumor before surgery, aiming to reduce intraoperative bleeding and facilitate safer tumor resection. The primary purpose of this study is to evaluate the technical feasibility, safety, and effectiveness of preoperative endovascular embolization in patients with highly vascular intracranial tumors. Participants enrolled in this prospective study will undergo: 1. Pre-procedural neurological and diagnostic cross-sectional imaging (contrast-enhanced MRI or CT angiography). 2. Diagnostic digital subtraction angiography (DSA) to map tumor-feeding arteries, followed by super-selective catheterization to deliver embolic materials (polyvinyl alcohol particles, Onyx, or microcoils). 3. Microsurgical tumor resection within 24 to 72 hours following the embolization procedure. Researchers will assess the degree of tumor devascularization achieved, the volume of intraoperative blood loss, blood transfusion requirements, total surgical duration, extent of tumor resection, and the occurrence of any procedure-related complications.

This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases.

This is a Phase I Study evaluating the safety and feasibility of IL-8 receptor-modified patient-derived activated CD70 CAR T cells in adult patients with brain metastases from primary cancer, with either newly diagnosed lesions or recurrent or progressive disease after prior therapy.

The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by the presence of brain metastasis (BM) and whose tumors have mutated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene.

This is a Phase II, single-arm, multicenter trial for patients with metastatic non-small cell lung cancer who have brain metastases and no known actionable mutations. Eligible patients will receive a combination of Datopotamab-deruxtecan, Carboplatin, and Pembrolizumab every three weeks for four cycles, followed by maintenance therapy with Datopotamab-deruxtecan and Pembrolizumab until disease progression or intolerable toxicity. Patients with intracranial progression but no systemic progression may receive stereotactic radiosurgery and continue treatment based on the investigator's decision.

This study is to evaluate the efficacy and safety of TY-9591 in first-line treatment of patients with EGFR-sensitive mutation-positive non-small cell lung cancer with brain metastases compared to Osimertinib.

This study evaluates whether review by the University of Kentucky Markey Cancer Center Neuro-Oncology Multidisciplinary Tumor Board improves clinical outcomes for adults with advanced brain metastases. Participants receive standard-of-care treatment as determined by their treating physicians. The study assesses whether multidisciplinary tumor board review and implementation of its treatment recommendations are associated with improved overall survival, progression-free survival, treatment selection and other clinical outcomes compared with patients who do not adhere to the tumor board recommendations.

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

Brain metastases are a source of much morbidity and mortality in adults with primary solid malignant tumors. With improvements in systemic therapy that prolong survival but have limited central nervous system penetration, patients with brain metastases are at increasing risk of developing and experiencing long-term side effects from treatment of brain metastases. The overarching goal of this study is to better understand the determinants of RT-associated changes in white and gray matter function and associated neurocognitive decline.

There is a lack of prospective trial data and consensus guidelines describing the use of Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of brain metastases. There has been no prospective dose escalation study performed to date to determine the maximum tolerated dose (MTD) in patients treated with FSRT. Prescription doses in the series described above ranged from 18 Gy to 42 Gy, delivered in 3 to 12 fractions. The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The investigator team thus proposes a Phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Radiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment.