Clinical Research Directory

Study of an AAV Mediated Dual-Payload Gene Therapy in Patients With High Grade Glioma

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.

Window Trial of Fluorescently Labeled Nivolumab-IRDye800 (Nivo800) in High Grade Glioma (HGG)

High-grade gliomas (HGGs) are among the most aggressive and treatment-resistant brain tumors. Immunotherapy with checkpoint inhibitors like nivolumab has shown promise, but its efficacy remains variable and poorly understood in this patient population. This clinical trial investigates a novel imaging-enabled formulation of nivolumab-IRDye800 (nivo800) which incorporates a near-infrared (NIR) fluorescent dye to enable real-time visualization of drug distribution within tumor tissue.

Pre-Radiation Chemotherapy for Newly Diagnosed High-Grade Glioma.

Better treatments are needed for high-grade gliomas (HGG), and new ways of treating this disease should be tested. The investigators want to see if giving medicine before radiation works well. After radiation, MRI scans can be harder to understand because radiation changes how the brain looks on the scan. If new medicines are given before radiation, the scans are easier to read. First, the investigators need to find out if giving chemotherapy early works using a drug we already know can treat gliomas. The investigators will start with temozolomide, which is the only chemotherapy approved by the FDA for HGG. If this approach is successful, the investigators can then test new drugs using this screening method.

Gallium Maltolate for the Treatment of Pediatric Patients With Relapsed or Refractory Pediatric High-Grade Glioma and Atypical Teratoid Rhabdoid Tumor

In this study, we want to find out more about the side effects of an investigational drug for relapsed or refractory atypical teratoid rhabdoid tumor and high-grade glioma, Gallium Maltolate (GaM) and what doses of GaM are safe for people to take. Everyone in this study will receive GaM which is still experimental and is not approved by the U.S. Food and Drug Administration. We do not know all the ways that this drug may affect people. We hope the information from this study will help us develop a better treatment for relapsed or refractory atypical teratoid rhabdoid tumor and high-grade glioma in the future.

Determine Maximum Tolerated Dose, Safety, and Tolerability of Rhenium (186Re) in Pediatric Recurrent, Refractory or Progressive Ependymoma and High-Grade Glioma

Pediatric patients 6-21 years of age with supratentorial recurrent, refractory, or progressive pediatric ependymoma and high-grade glioma (HGG) will be included in this study of treatment with Rhenium-186 Nanoliposome (186RNL). Phase 1 of the study will look to determine the maximum tolerated dose (MTD) of 186RNL in this patient population. Phase 2 of the study will use the recommended dose determined in Phase 1 to continue to look at overall response rate and progression-free survival following 186RNL treatment.

A Phase 0/1 Study of cDNA for TP53, Checkpoint Inhibition and Radiation in Children With Recurrent, Progressive or Refractory CNS Malignancies.

This clinical trial is studying a drug called SGT-53 along with radiation and another drug called Nivolumab. It's for children with brain tumors that have come back, gotten worse, or didn't get better with earlier treatments. The main questions it aims to answer are: What is the right dose of SGT-53 that children can safely receive when it is used with radiation and Nivolumab? This dose will be used in the second phase of the trial. What side effects are there of SGT-53 when it is used with radiation and Nivolumab? How does SGT-53 move through the body when given with radiation and Nivolumab? How much of the SGT-53 drug is found in the tumor tissue? This will be tested in a small group of patients? Participants will: For the first treatment cycle: Get SGT-53 twice per week Get Nivolumab every 2 weeks Receive radiation therapy during week 2 For Cycles 2-6: Get SGT-53 once per week during even cycles and twice per week during odd cycles Get Nivolumab every 2 weeks For Cycles 7+ Get both SGT-53 and Nivolumab every 2 weeks In the phase 0 part of the study, 4 participants will have genetic testing performed on their tumor tissue after receiving SGT-53. These samples will be compared to another sample taken from the skin.

Feasibility of Aspirate Tissue Monitoring in Neuro-oncological Surgery

Gliomas are tumors that occur in all ages; they include the most common malign primary central nervous system tumors in developed countries. Gliomas are often aggressive, and their recommended treatment is surgical resection and chemoradiation. Complete tumor removal is challenging because of diffuse cell growth and the proximity of functionally critical tissues. Surgeons use 5-aminolevulinic acid (5-ALA) drug-induced fluorescence to visually detect tumor cells, which improves resection rates and delays tumor progression. Tumor cells are often left unnoticed because of visual obstacles or weak fluorescence, which may lead to local recurrence and reoperations. Surgical suction devices are used to remove cancerous tissues, but so far the suction aspirate tissues have not been routinely used in tissue detection. This multicenter controlled clinical trial investigates the clinical performance and outcomes of a new method for detecting tumor from the suction aspirates in near-real time based on 5-ALA induced fluorescence. The feedback from the aspirate tissue monitor (ATM) is expected to improve the identification of tumors, leading to fewer reoperations and better treatment outcomes.

Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined with the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).

Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)