Glioma

Researchers are evaluating the safety of increasing doses of 131I-TLX101 given intravenously alongside standard care in patients newly diagnosed with glioblastoma, a type of brain tumor. This open-label, single-arm, multicenter Phase 1 study focuses on patients with histologically confirmed glioblastoma who have undergone surgery but not yet received systemic or radiation therapy. Participants receive ascending doses of 131I-IPA intravenously via infusion combined with the best standard of care, including planned chemoradiation therapy starting 3 to 6 weeks after surgery. The study monitors safety and dose-limiting toxicities over multiple dose levels to identify the recommended Phase 2 dose. During the 62-week study, participants undergo regular evaluations including clinical assessments, lab tests such as liver function, and monitoring for treatment-emergent adverse events. Researchers measure the incidence and severity of dose-limiting toxicities from the first dose until discharge after the second dose, along with overall safety and tolerability throughout the study period.

Researchers are evaluating the use of 18F-DOPA PET/CT imaging to improve the detection and assessment of various conditions including congenital hyperinsulinism, neuroblastoma, neuroendocrine tumors, Parkinson's disease, Lewy body dementia, and brain tumors. This phase III prospective cohort study aims to optimize imaging by assessing new digital PET/CT technology and the effect of intravenous furosemide on image quality, particularly in the pelvis. Additionally, the study investigates gallbladder activity patterns and explores possible links between brain and gallbladder dopaminergic denervation. Participants will receive an intravenous injection of 18F-DOPA at a dose of 4MBq/kg (minimum 110 MBq, maximum 600 MBq). Some patients will also be given a single intravenous dose of 40mg furosemide before imaging to improve scan quality. Imaging will be performed using a new PET/CT scanner with digital detectors and advanced reconstruction algorithms. A subgroup will undergo dynamic abdominal scans to study gallbladder activity over time. The study plans to enroll 800 patients over about five years, with approximately 160 scans yearly. During the study, researchers will measure lesion size and activity, bladder activity and artifacts, and gallbladder uptake at multiple time points. Participants will complete questionnaires about gallbladder disease history. Imaging results will be compared to previous scans for quality assessment. The study includes safety monitoring and clinical interpretation of scans, with results shared with referring physicians. Participation involves a single PET/CT scan session lasting about 20-30 minutes, with additional dynamic imaging for some patients.

Researchers are evaluating the use of 18F-Fluciclovine positron emission tomography (PET) to monitor brain metastases in adults treated with stereotactic radiosurgery (SRS). This pilot imaging study focuses on whether 18F-Fluciclovine PET can serve as a biomarker to measure tumor response or progression after SRS in patients with brain metastases. The trial is a phase 1 study involving participants with diagnosed brain metastases from cancer. Participants will receive a 5-mCi dose of 18F-fluciclovine administered intravenously just before PET scanning. PET imaging will be performed up to 25 minutes after injection, capturing both static images from 10 to 20 minutes and dynamic series divided into four 5-minute frames from 5 to 25 minutes post-injection. This imaging approach allows for assessment of movement and time-dependent changes in the brain metastases. During the study, participants will undergo PET scans to measure changes in standardized uptake values (SUV-peak, SUVmean, and SUVmax) over 8 weeks. The study will include assessments such as MRI scans and safety monitoring. Participants must adhere to contraception requirements if of reproductive potential and avoid breastfeeding temporarily if applicable. The overall goal is to determine the ability of 18F-Fluciclovine PET to track treatment effects following SRS in brain metastasis patients.

Researchers are evaluating the use of 18F-fluciclovine (Axumin®) PET imaging to help manage children with high-grade gliomas (HGG), including diffuse midline glioma (DMG). The study aims to determine if this imaging technique can safely and effectively distinguish between true tumor growth (progression) and other changes in the tumor that can happen after treatment, which is important for guiding clinical decisions. Participants will receive an injection of 18F-fluciclovine through an IV before undergoing a combined PET-MRI scan. This imaging procedure is being studied as a diagnostic tool to better differentiate true tumor progression from post-treatment changes, which conventional MRI cannot reliably do. The evaluation includes participants both with and without planned surgery or biopsy. Throughout the study, participants will undergo image analysis at 6 months and histopathology analysis at 4 weeks. Researchers will monitor safety and effectiveness of the imaging, assess tumor progression, and compare findings with post-treatment changes. Participation involves multiple assessments over time to gather detailed information on the imaging's diagnostic value in pediatric high-grade glioma management.

Researchers are evaluating amivantamab, an investigational drug, in patients with high-grade malignant brain tumors, specifically glioblastoma multiforme (GBM) and related molecular subtypes. This Phase 1b trial aims to assess the safety, tolerability, and preliminary antitumor activity of amivantamab when given at the recommended Phase 2 dose. The study is part of the Minderoo 5G platform, focusing on biomarker-guided therapies for patients with molecularly defined brain tumors characterized by EGFR amplification and other genetic markers. Amivantamab is given as an intravenous infusion weekly for the first 4 weeks, followed by every 2 weeks until disease progression or unacceptable side effects occur. The initial dose is split over two days to improve tolerance, starting with 350 mg over 4 hours and then 1400 mg over 6 hours. Subsequent doses are 1750 mg over 2-5 hours in the first cycle and 2-3 hours thereafter if well tolerated. The trial includes an adaptive design with decision points led by a Safety Review Committee to guide further study steps and progression to Phase 2 depending on emerging data. Participants will undergo regular evaluations including clinical assessments, laboratory tests, and imaging to monitor tumor response and safety over an 18-month period. Researchers will measure safety outcomes and preliminary efficacy using established criteria for tumor response. Patients must meet specific eligibility criteria related to diagnosis, previous treatments, and general health status. The study also includes monitoring for side effects and adherence to study protocols throughout participation.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of paxalisib combined with temozolomide in patients with high grade malignant brain tumours, specifically glioblastoma. This Bayesian multi-centre, multi-arm, open-label, adaptive Phase 1/2 trial focuses on molecularly defined biomarker arms, including patients with hyperactivating PI3K mutations or PTEN loss. The study aims to provide proof-of-concept molecular hypothesis testing within the 5G platform for patients with these aggressive brain tumours. During Phase 1b, patients will be treated with paxalisib starting at 45 mg once daily, with an option to increase the dose in the second cycle. Temozolomide will be given orally once daily on days 1 to 5 of a 28-day cycle, starting at 150 mg/m2 with possible escalation to 200 mg/m2 after the second cycle if well tolerated. Each biomarker arm will enroll 10 patients in parallel during Phase 1b, with up to 32 patients recruited across Phase 1b and Phase 2 if initial safety and efficacy decisions support continuation. Participants will undergo regular monitoring for safety and antitumour activity over 12 months in Phase 1b and up to 24 months in Phase 2. Assessments include clinical evaluations, biomarker analysis, and imaging to measure treatment effects. The study emphasizes tracking adverse events, tolerability, and tumour response to the investigational combination therapy, with ongoing review by a Safety Review Committee to guide study progression and patient safety.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of the investigational drugs avutometinib and defactinib in patients with malignant brain tumors, specifically glioblastoma and other molecularly defined high-grade brain tumors. This Phase 1/2 trial is part of the Minderoo 5G platform and includes biomarker-guided treatment arms targeting tumors with specific genetic features such as hyperactivating BRAF mutations or NF1 loss. The study uses a Bayesian multi-arm, open-label, adaptive design for efficient hypothesis testing and patient assignment. In the Phase 1b portion, patients with relapsed glioblastoma multiforme (GBM) receive double therapy with oral avutometinib at 3.2 mg twice weekly (total 6.4 mg per week) and oral defactinib at 200 mg twice daily (total 400 mg per day). Treatment arms progress to Phase 2 upon meeting predefined success criteria, where efficacy is tested in the front-line minimal residual disease setting. Phase 2 may involve doublet therapy or triplet therapy adding temozolomide capsules, given either concurrently or sequentially based on emerging data and safety review committee decisions. Participants undergo screening and assessments including molecular tumor profiling, neurological evaluations, and laboratory tests before and during treatment. Researchers monitor safety, tolerability, and tumor response over 9 to 12 months depending on the phase. The trial includes ongoing safety reviews and adaptive decision points to guide treatment continuation or modification. Participant involvement includes oral medication administration, clinical follow-up, and data collection on tumor activity and side effects throughout the trial duration.

Researchers are investigating the use of Ga-68-DOTATATE PET/MRI scans in diagnosing and managing patients with somatostatin receptor-positive central nervous system (CNS) tumors, mainly meningiomas, but also including other tumors like esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and certain brain metastases from systemic cancers. This study aims to determine if Ga-68-DOTATATE PET/MRI can better distinguish tumor recurrence from post-treatment changes, improving diagnosis and treatment planning. The investigation builds on prior pilot data showing promising results in detecting residual tumor and additional lesions not visible on MRI alone. Participants with meningioma who are planning surgery will have a Ga-68-DOTATATE PET/MRI scan combined with their standard care MRI before surgery for research purposes. Up to two additional follow-up PET/MRI scans may be performed as part of standard care. For patients with other somatostatin receptor-positive CNS tumors, PET scans may be added to their routine MRI to assess disease extent. When necessary, 1.5 Tesla MRI combined with PET/CT fusion imaging may be used instead of 3 Tesla MRI. During the study, participants will undergo these imaging procedures and clinical evaluations over time to assess the usefulness of Ga-68-DOTATATE PET/MRI in their care. Researchers will follow participants longitudinally, up to 10 years, to evaluate whether the scans provide additional clinical benefit in monitoring tumor status. Safety monitoring and diagnostic assessments will be conducted throughout the study to ensure accurate and informative results.

Researchers are evaluating the use of 68Ga-NOTA-RM26, a PET tracer that targets the gastrin-releasing peptide receptor (GRPR), to diagnose high-grade glioma and predict glioma grade using PET/CT scans. GRPR is a receptor found in various tumors, including glioma, and this study aims to assess the clinical value of this imaging method in patients with suspected or confirmed untreated glioma. This is an early phase 1, open-label study focusing on brain PET/CT imaging in glioma patients. Participants will receive a single intravenous injection of 68Ga-RM26 in doses ranging from 74 to 185 MBq (2-5 mCi). This tracer is designed to bind to GRPR in tumor cells, allowing PET/CT scans to image glioma lesions effectively. The study involves one treatment administration and subsequent imaging to evaluate the tracer's ability to visualize glioma. During the study, participants will undergo PET/CT scans to measure the maximum standardized uptake value (SUVmax) over an average period of 1.5 years. Researchers will monitor the imaging results to determine the tracer's diagnostic accuracy and correlation with glioma grade. Participant safety and compliance will be observed throughout the study period, with follow-up assessments as needed to complete the evaluation.

This research investigates a new dual-target molecular imaging technique using the agent 68Ga-RM26-RGD for PET/CT scans in patients with tumors that express GRPR and integrin αvβ3 receptors, such as breast, brain, and prostate cancers. The study aims to improve tumor visualization by overcoming limitations of conventional single-target imaging methods like 18F-FDG PET/CT, which may have low uptake in some tumors. This early phase 1 trial evaluates the clinical usefulness of this novel imaging approach compared to traditional and single-target agents. Participants will receive intravenous injections of 68Ga-RM26-RGD at a dose of about 1.8-2.2 MBq/kg. The study compares this dual-target agent with conventional 18F-FDG and single-target agents 68Ga-RM26 and 68Ga-RGD in PET/CT imaging. Each participant undergoes imaging with these agents within a two-week period to assess diagnostic performance and tumor detection capabilities. During the study, researchers will monitor diagnostic accuracy over approximately one year. Participants will undergo multiple PET/CT scans, and the study will collect data on imaging performance to evaluate how well the agents detect tumors. Safety and compliance will be monitored throughout, with written informed consent required before participation. This study helps to understand the value of dual-target imaging in detecting certain cancers more effectively than current methods.