Glioma

Researchers are evaluating the safety and appropriate dose of increasing levels of the radioactive drug 131I-TLX101, given by intravenous infusion, combined with the best standard care in adults newly diagnosed with glioblastoma, a type of brain cancer. This open-label, single-arm study is conducted across multiple centers and aims to understand how patients tolerate this treatment alongside standard therapies. Participants receive escalating doses of 131I-TLX101 through an intravenous infusion along with the standard chemoradiation therapy known as the Stupp regimen, beginning 3 to 6 weeks after surgical removal of the tumor. The study includes a dose-finding phase to establish the recommended dose, with safety monitored throughout. The radioactive drug is administered in ascending doses, and the study observes participants for up to 62 weeks. During the study, participants will undergo regular safety assessments including laboratory tests of liver and kidney function, monitoring for adverse events, and evaluations of treatment-related toxicities for up to 62 weeks. Researchers will track the incidence and severity of dose-limiting toxicities and treatment-emergent adverse events. Participants must comply with radiation safety guidelines and attend scheduled visits for monitoring. The total study duration from screening until the end is about 62 weeks.

Researchers are evaluating the optimization of 18F-DOPA PET/CT imaging in specific patient groups including pediatric patients with congenital hyperinsulinism or neuroblastoma, pediatric and adult patients with neuroendocrine tumors or brain tumors, and adults suspected of Parkinson's disease or Lewy body dementia. The study aims to improve image quality using a new digital PET/CT scanner and intravenous furosemide, while also exploring gallbladder activity patterns related to dopaminergic degeneration. Participants will receive an intravenous injection of 18F-DOPA, with some also receiving a single intravenous dose of furosemide. The study includes a primary objective of assessing image quality improvements in the pelvis area and a secondary objective examining gallbladder activity patterns using dynamic imaging in a subgroup. Imaging data will be compared to previous scans with older technology. During the study, participants will undergo PET/CT scans, with measurements of lesion size and activity, bladder activity, and image artifact scoring. A questionnaire will screen for gallbladder disease history. The research team will analyze the imaging results and gallbladder activity patterns, with follow-up assessments occurring within one to three months. The total planned enrollment is 800 patients over approximately five years, with detailed monitoring of image optimization and gallbladder activity.

Researchers are evaluating the use of 18F-Fluciclovine positron emission tomography (PET) as a biomarker to measure the response or progression of brain metastasis in participants treated with stereotactic radiosurgery (SRS). This pilot imaging study focuses on adults diagnosed with brain metastases who are planned to receive SRS treatment. The study is sponsored by Baptist Health South Florida and is a Phase 1 clinical trial. Participants will undergo an 18F-fluciclovine PET scan at the time of their SRS planning magnetic resonance imaging (MRI). They will then receive a single dose of SRS as part of their standard care. A second 18F-fluciclovine PET scan will be performed approximately 8 weeks after the SRS treatment, with a window of plus or minus 2 weeks. During PET scans, participants receive a 5-mCi dose of 18F-fluciclovine through intravenous injection, with imaging data collected up to 25 minutes post-injection. Throughout the study, participants will be monitored using PET imaging to evaluate changes in standardized uptake values (SUV) over 8 weeks, which helps assess tumor response. Tumor control will also be evaluated at 12 months. The study involves standard imaging, including MRI and PET scans, and tracks participant safety and treatment progress. Total participation timelines include initial scans at SRS planning and follow-up imaging about 8 weeks later, with tumor control assessed after one year.

Researchers are evaluating whether 18F-fluciclovine (Axumin®) PET imaging can help doctors distinguish between true tumor growth and other changes in children with high-grade gliomas, including diffuse midline glioma. This distinction is important because true tumor progression may require a change in treatment, while post-treatment changes usually do not. Conventional MRI scans cannot reliably make this differentiation, so this study aims to see if 18F-fluciclovine PET imaging can serve as a useful diagnostic tool. Participants will receive a single intravenous injection of 18F-fluciclovine before undergoing a combined PET-MRI scan. This imaging process is designed to assess tumor status by detecting physiological changes. The study focuses on children and young adults aged 1 to under 21 years with measurable high-grade gliomas or diffuse midline gliomas. The study is an early phase 1 trial, and treatment involves only this one-time imaging procedure. During the study, researchers will analyze the imaging results and compare them to histopathology findings within four weeks and evaluate safety over six months. Participants will be monitored for any side effects related to the imaging agent. The study will assess the usefulness and safety of 18F-fluciclovine PET-MRI in guiding treatment decisions for pediatric high-grade glioma. Participation lasts through these assessments, with imaging and follow-up evaluations scheduled accordingly.

Researchers are evaluating the safety and tolerability of amivantamab, an investigational drug, in patients with high grade malignant brain tumours such as glioblastoma. This Phase 1b trial focuses on a biomarker-defined group of patients whose tumours show EGFR amplification. The study aims to determine the preliminary anti-tumour activity of amivantamab administered at the recommended Phase 2 dose, with decisions guided by adaptive trial design and safety review committees. Amivantamab will be given by intravenous infusion weekly for the first 4 weeks, then every 2 weeks thereafter until the disease progresses or unacceptable side effects occur. The initial dose is split over two days, with subsequent doses given over 2 to 5 hours initially and shorter infusions if well tolerated. This Phase 1b biomarker arm will enroll 12 patients with relapsed glioblastoma to assess treatment effects. Participants will undergo regular monitoring including whole genome and transcriptome data collection as part of the Minderoo Precision Brain Tumour Programme. Safety and tumour response will be closely assessed through clinical evaluations and imaging over an 18-month period. The main outcomes measured are safety, tolerability, and preliminary anti-tumour activity, with additional analysis of molecular markers related to treatment response.

Researchers are evaluating the safety, tolerability, and preliminary antitumor activity of paxalisib combined with temozolomide in patients with high-grade malignant brain tumors, including glioblastoma. This Phase 1b and Phase 2 study is part of the 5G-PEARL trial, which uses biomarker-guided approaches to treat tumors with specific genetic changes such as PI3K mutations or PTEN loss. The study aims to test these treatments in molecularly defined patient groups to better understand their effects. The study includes two parts: Phase 1b focuses on safety and early activity, while Phase 2 assesses effectiveness further. In Phase 1b, patients receive paxalisib starting at 45 mg once daily, with a possible increase to 60 mg per day in Cycle 2. Temozolomide is taken orally once daily on days 1 to 5 of each 28-day cycle, starting at 150 mg/m2 with potential dose increase to 200 mg/m2 from Cycle 3 if tolerated. The trial enrolls patients into two biomarker arms based on tumor genetics, with adaptive decision points to guide study progress. Participants will have assessments including safety monitoring and genetic biomarker analysis over up to two years, depending on the phase. Researchers measure treatment-emergent adverse events and antitumor activity as primary outcomes. Quality of life and additional biomarker responses are also evaluated. Patients will be monitored regularly through clinical visits and tests to track treatment effects and side effects throughout the study duration.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of two investigational drugs, avutometinib and defactinib, in patients with high grade malignant brain tumours, including glioblastoma (GBM). This Phase 1/2 clinical trial uses biomarker-guided approaches to target specific molecular subtypes of brain tumours. The study is part of the Minderoo 5G platform and includes patients with relapsed or frontline minimal residual disease (MRD) settings. In Phase 1b, patients with relapsed GBM will receive oral avutometinib at a dose of 3.2 mg twice weekly and defactinib at 200 mg twice daily after meals, aiming for a total weekly dose of 6.4 mg and daily dose of 400 mg respectively. Phase 2 will test the antitumour activity of these drugs given at the recommended dose, either as a doublet or combined with temozolomide, depending on earlier results. Treatment will be given in molecularly defined biomarker arms, with decisions guided by safety and efficacy data. Participants will undergo assessments for safety, tolerability, and tumour response over 9 to 12 months. Molecular profiling will help identify response markers, and quality of life will be monitored during Phase 2. Patients must consent to genomic testing and will be followed regularly with clinical evaluations. The study includes rigorous monitoring for side effects and disease progression, with a total participation duration aligned with treatment phases and follow-up.

Researchers are evaluating the use of Gallium-68-DOTATATE PET/MRI in patients with somatostatin receptor-positive (SSTR-positive) central nervous system (CNS) tumors, mainly focusing on meningioma but also including other tumor types such as esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain. The study aims to assess the diagnostic usefulness of this imaging technique, especially in distinguishing tumor recurrence from post-treatment changes, with a particular interest in cases where tumor location limits surgical removal or where patients have higher-grade disease or previous radiation treatment. This is a Phase 4 interventional study sponsored by Weill Medical College of Cornell University.

Researchers are evaluating a new dual-target imaging agent called 68Ga-RM26-RGD for PET/CT scans in patients with breast, brain, and prostate cancers that express specific receptors (GRPR and integrin αvβ3). This study aims to improve tumor detection by comparing this agent with conventional 18F-FDG and single-target imaging agents, addressing limitations of current imaging methods in detecting tumors with low 18F-FDG uptake or variable receptor expression. Participants will undergo PET/CT scans using intravenous injections of 68Ga-RM26-RGD and one of the comparator agents (18F-FDG, 68Ga-RM26, or 68Ga-RGD) within a two-week period. The dosages for these agents are approximately 1.8-2.2 MBq/kg. Each patient receives scans with both agents to compare imaging performance directly. During the study, researchers will assess diagnostic accuracy and dosimetry of 68Ga-RM26-RGD over about one year. Participants will have multiple PET/CT scans and related evaluations to monitor uptake of the imaging agents in tumors. The study includes safety and diagnostic performance monitoring throughout the participation period.

Researchers are evaluating 68Ga/177Lu-PSMA theranostics as a treatment option for patients in Norway with recurrent grade 3 and grade 4 gliomas, which are aggressive brain tumors. The study aims to improve current diagnostic and treatment methods for glioma patients, focusing on a new radionuclide therapy that may help improve survival and quality of life for patients who currently have limited options and short expected survival. This pilot interventional study seeks to introduce this novel approach in clinical practice. Patients who show high tumor uptake of 68Ga-PSMA on a PET/MRI scan during screening may receive 177Lu-PSMA radionuclide therapy. Participants typically receive three treatment cycles, with the possibility to extend up to six cycles. After each treatment cycle, SPECT/CT scans are used for dosimetry calculations. Throughout the treatment and for up to 1.5 years after starting therapy, researchers will monitor patients with PET/MRI scans, quality-of-life questionnaires, and clinical exams to assess the therapy's effects. Participants will be involved in regular imaging and clinical evaluations, including PET/MRI and SPECT/CT scans, quality-of-life assessments, and performance status checks. Researchers will track progression-free survival, overall survival, and adverse events up to six months after therapy concludes. The study also evaluates radiation doses to tumors and critical organs, tumor response, and changes in PSMA uptake to understand treatment effects and safety over time.