Clinical Research Directory

Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII

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?

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.

New Adjuvant Vaccine in Glioblastoma, a Phase 1/2a Study

This phase I/II trial evaluates the safety and the immunological efficacy of a cancer vaccine against 2 glioma-associated antigens in newly-diagnosed glioblastomas. The objectives of this study are as follows: Primary objective * phase 1: * to assess the maximum tolerated dose (MTD) and select the recommend Phase 2a dose * phase 2a: * to assess anti- TERT specific T cell responses at 2 months at the selected dose level Secondary objectives: * To assess Short and long-time immunological safety * To assess Evolution of anti-PTPRZ1 and anti-TERT immune T cell responses over time * To assess Progression free survival (RANO 2.0 criteria) * To assess Overall survival * To assess Quality of life by EORTC QLQ30 and BN20 questionnaires as well as objective of ancillary study: to determine the mechanism of action of potential tumour escape in GBM (T-cell lymphocyte phenotype; antigen expression and checkpoint inhibitors on tumour cells at relapse, if available), analysis of circulating antibodies against TERT epitope and/or melanin, and identification of predictive biomarkers of response. Ultimately, this trial together will lead to the implementation of future phase III trial in GBM. All patients enrolled in the study will receive standard treatment consisting of surgical resection of the tumor followed by radio-chemotherapy. Immunotherapy will begin 4 weeks after the completion of radiotherapy.

A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors

This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in patients with advanced solid tumors. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab

GIANT is an open-label, multi-center, randomized, perioperative (neoadjuvant followed by adjuvant), phase 2 trial with a safety lead-in phase to investigate the feasibility, safety and tolerability, and establish the biological activity of nivolumab with or without relatlimab in patients with isocitrate dehydrogenase (IDH) wildtype newly diagnosed glioblastoma (ndGBM).

BRiTE - Bispecific T Cell Engager for Patients With Glioblastoma

This Phase 1 study will assess the safety of a novel brain Bispecific T cell engager (BRiTE) in patients with newly diagnosed or recurrent World Health Organization (WHO) Grade 4 glioblastoma (GBM). Owing to its short half-life, the study drug, BRiTE, will be continuously infused intravenously (IV) for 4 days (96 hours) in a 28-day cycle. Given that BRiTE specifically exerts its effects on tumor cells expressing the Epidermal Growth Factor Receptor variant III (EGFRvIII) mutation, we will only enroll patients with EGFRvIII-positive tumors in this study. The primary objective is to evaluate the safety and tolerability of continually infused BRiTE in ndGBM and rGBM patients and determine the maximum tolerated dose (MTD) for continuously infused BRiTE.

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB. The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.

Mycophenolate Mofetil Combined With Radiation Therapy in Glioblastoma

This is a phase 0/1 dose-escalation trial to determine the maximum tolerated dose of Mycophenolate Mofetil (MMF) when administered with radiation, in patients with glioblastoma or gliosarcoma.

Personalized Cancer Stem Cell High-Throughput Drug Screening for Glioblastoma

Proposed treatment of subjects with newly diagnosed glioblastoma with novel personalized drug regimens identified to be effective in vitro using cancer stem cells derived from their individual tumors, alongside standard of care radiation and TMZ.

Pembrolizumab for Newly Diagnosed Glioblastoma

The study explores the addition of pembrolizumab to temozolomide-based radiotherapy in patients with newly diagnosed glioblastoma.

A Study to Evaluate the Efficacy and Safety of TJ107 in Lympopenic Patients With Newly Diagnosed Glioblastoma Who Completed Standard Concurrent Chemoradiotherapy (CCRT)

A Phase 2, Randomized, Single-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TJ107 in Lympopenic Patients with Newly Diagnosed Glioblastoma Who Completed Standard Concurrent Chemoradiotherapy (CCRT)

The Assessment of Immune Response in Newly Diagnosed Glioblastoma Patients Treated With Pembrolizumab

To evaluate the short-term and longer-term safety, tolerability, and effectiveness of neoadjuvant and adjuvant Pembrolizumab on top of standard therapy (Stupp protocol) in patients with Glioblastoma Multiforme (GBM). Randomized comparison of safety, tolerability, and clinical efficacy of (1) neoadjuvant and adjuvant Pembrolizumab (on top of Stupp protocol, n=12 patients), (2) neoadjuvant Pembrolizumab (on top of Stupp protocol, n=12 patients), and (3) standard of care (Stupp protocol only, n=12 patients). Immuno-PET examination will be performed before and after surgery in all patients.