Glioblastoma clinical trials — recruiting now

This study was designed to evaluate the safety, tolerability, efficacy and pharmacokinetics of JK-1201I combined with adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme after surgery and concomitant radio-chemotherapy.

WinGlio is a phase I study investigating neoadjuvant (before surgery) ipilimumab ( a type of immunotherapy drug) in patients with newly diagnosed glioblastoma (a form of brain cancer). Participants will receive up to 2 cycles of ipilimumab prior to the standard of care treatments for this patient group which can include debulking surgery and chemoradiation. The aim of giving the ipilimumab to the participants is to see if it is safe to treat patients with this condition with ipilimumab and also to see if the drug helps to reduce or control the patient's disease.

The purpose of this study is to assess the feasibility, safety and efficacy of Delta-like ligand 3 (DLL3)-specific CAR-T cell therapy in patients with DLL3 positive brain tumors including glioblastomas and diffused intrinsic pontine or midline gliomas (DIPG or DMG). Another goal of the study is to learn more about the function of the anti-DLL3 CAR-T cells and their persistency in patients.

The purpose of this clinical trial is to evaluate the safety and tolerability of paxalisib in combination with temozolomide and to determine the preliminary antitumour activity of the combination therapy. In the Phase 1b of this study parallel biomarker defined arms will be opened in the front-line unmethylated MGMT setting, enrolling 10 patients onto each arm. These patients will be treated with paxalisib in combination with temozolomide (TMZ). The starting dose of paxalisib will be 45mg once a day (OD) with the option of increasing to 60 mg (30 mg BD) in Cycle 2. TMZ will be administered once daily by mouth on days 1 to 5 in a 28-day cycle, with a starting dose of 150mg/m2 during cycles 1 and 2, and subsequent dose escalation to 200mg/m2 at the start of cycle 3 if cycles 1 and 2 have been well tolerated with no significant toxicity.

The goal of this clinical trial is to learn if DOC1021 + pIFN alongside standard of care (SOC) will improve survival in adult patients newly diagnosed with glioblastoma (IDH-wt). It will also evaluate the safety of DOC1021 + pIFN. Researchers will compare DOC1021 dendritic cell immunotherapy regimen added to SOC compared to SOC treatment alone. Participants in the DOC1021 + pIFN + SOC arm will: * Take filgrastim subcutaneously x 5 doses and subsequently undergo a leukapheresis collection * Undergo ultrasound guided perinodal DOC1021 injections every 2 weeks for a total of 3 doses * Receive subcutaneous pIFN injections weekly for a total of 6 doses in parallel with the DOC1021 injections Both arms of the trial will: \- Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive SOC treatment with surgery, temozolomide chemotherapy and radiation

The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.

This study is an open-label, single-arm Phase I/II clinical trial with the primary objective of evaluating the safety, tolerability, and efficacy of VRT106 in patients with recurrent/progressive 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.

This study is investigating the use of a computer algorithm to analyze scans of the brain before surgery to predict how a person's tumor will respond to treatment.

This trial is a translational, open-label, monocentric prospective study of 80 patients aiming to study resistance mechanisms as well as biomarkers of resistance or sensitivity to TTFields. The study will be conducted on a population of patients with newly diagnosed glioblastoma treated with radio-chemotherapy followed by TTFields in the context of either routine care or a clinical trial. In this study, the Optune® system (battery operated device which delivers TTFields to the brain) will not be under investigation. For each included patient, blood samples will be collected during baseline visit (before initiation of radio-chemotherapy), then before initiation of TTFields and every 3 months during TTFields treatment. Additional blood samples will be scheduled at recurrence (if applicable). Moreover, tumor samples (formalin paraffin embedded (FFPE) tumor block and fresh samples) will be collected from surgery specimen on primary tumor by the sponsor for analysis. In case of recurrence, and if a second surgery is possible, tumor samples will also be collected. Tumor samples will be collected from biopsies taken in the course of routine practice and from surgical specimens collected during surgical procedure. No additional biopsies will be performed for the study. Patients will be followed-up for time to progression and overall survival for a maximum duration of 24 months from the TTFields initiation. MRI performed by patients during the course of the study will be collected by the sponsor for additional future research purposes.

This phase I/II trial studies the side effects and best dose of Visudyne (liposomal verteporfin) and to see how well it works in treating patients with high grade EGFR-mutated glioblastoma that has come back (recurrent). Visudyne is FDA approved in combination with light to treat eye diseases. In this study we use Visudyne by itself like chemotherapy to kill tumor cells which may be sensitive to verteporfin.

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.

This clinical trial evaluates the use of microdialysis catheters during surgery to collect biomarkers, and studies the feasibility of intraoperative microdialysis during neurosurgery for central nervous system malignancies. A biomarker is a measurable indicator of the severity or presence of disease state. Information collected in this study may help doctors to develop new strategies to better diagnose, monitor, and treat brain tumors.

This is a phase 1 study evaluating the safety and feasibility of laser interstitial thermal therapy (LITT) followed by lomustine (CCNU) for recurrent glioblastoma in adults. The primary aim is to evaluate the safety of the combination of LITT plus lomustine based on the assessment of treatment-related adverse events and the feasibility of completing LITT + lomustine in the proposed timeframe. The secondary aim is to assess overall survival for up to 2 years after the first dose of lomustine.

EVIDENT's aim is to test if ex vivo drug screening can predict whether patients with solid cancers will respond, or not respond, to standard care treatments. Patients undergoing standard care surgery to excise their tumour, those undergoing a biopsy, or those having a fluid aspirate of a solid tumour with surplus tissue available after diagnostic use will be eligible for this study. The specimen will then be assessed with ex vivo drug screening utilising all standard therapies and therapies that are more novel and in early stages of development. The results of the ex vivo drug screen will be compared to the cancer's actual response to standard care treatments for those that undergo therapy to determine how effective the test is at predicting treatment response.

The clinical investigation is a non-randomized, multicenter, open-label, prospective, exposure-time escalation clinical investigation. The clinical investigation is designed to assess the clinical safety and performance of the Oncomagnetic Device.

Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This pilot study will evaluate the safety and feasibility of combining an investigational drug called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial approach is called sonodynamic therapy (SDT), and this investigational therapy is being tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for recurrent GBM.

MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of genes and, consequently, of intracellular signalling pathways that govern cellular behaviour (Komatsu et al., 2023). They are widely implicated in oncogenesis, and in particular in mechanisms promoting cell migration, invasion and proliferation (Romano et al., 2021). Several preliminary studies have shown that serum levels of pro-oncogenic microRNAs correlate with tumor rates in gliomas (Jones et al., 2021; Levallet et al., 2022; Morokoff et al., 2020). Morokoff's study showed encouraging but insufficient results on the possibility of using microRNAs to differentiate radionecrosis versus recurrence. These results need to be consolidated prospectively, with homogeneous samples taken from all patients. The aim of this study is to describe the evolution over time of plasma levels of pro-oncogenic microRNAs, after surgery for grade 4 glioma, in order to assess whether they can be used to identify false-positive recurrences on MRI (radionecrosis).

The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.

Current standard of care therapy and all FDA approved adjuvant therapy for glioblastoma continue to provide less than 12 months of progression free survival (PFS) and less than 24 months of overall survival (OS). There is an extreme need for any novel therapy against glioblastoma that increases progression free survival and overall survival in patients diagnosed with this invasive form of cancer. A significant reason for such a poor prognosis is the infiltrative nature of this tumor in non-enhancing regions (NE) beyond the central contrast-enhancing (CE) portion of tumor, which is difficult to visualize and treat with surgical, medical, or radiotherapeutic means. Since tumor cells exhibit abnormal metabolic behavior leading to extracellular acidification, we theorize a newly developed pH-sensitive MRI technique called amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) may identify infiltrating NE tumor beyond what is clear on standard MRI with gadolinium contrast. This phase I safety study will use use intraoperative CEST-EPI guided resections in glioblastoma at increasing distances from areas of CE tumor to test whether this technique is safe and can remove additional areas of infiltrative NE tumor. The primary objective of this study is to assess the safety of pH-sensitive amine CEST-EPI guided resections for glioblastoma.The secondary objectives of this study include: 1. A preliminary efficacy analysis of CEST-EPI guided resections in extending progression free and overall survival. 2. To confirm that resected tissue obtained from pH-sensitive amine CEST-EPI guided resections contain infiltrating NE tumor. The primary endpoint for this study will be safety of resecting "CEST positive", acidic regions within T2 hyperintense regions of glioblastoma thought to contain active NE tumor at increasing distances from contrast enhancing tumor with development of a recommended maximal tolerated resection. 1. At the maximal tolerated resection, a preliminary efficacy study with endpoints of progression free survival (as defined by RANO Resect 2.0) 1 and overall survival. 2. Quantitation of infilitrating tumor burden on CEST-EPI resected tissue using immunohistochemical staining. 12 patients up to 24 patients based on resection limiting toxicities with potential expansion of up to 16 patients at the maximum tolerated resection. Inclusion Criteria: 1. Must be able to provide written informed consent 2. Male or female \> 18 years of age 3. Karnofsky Performance Scale (KPS) \> 70 (indicating good performance status). 4. Individuals with suspected, newly diagnosed or recurrent IDH wild type WHO IV glioblastoma (intraxial, expansile contrast-enhancing mass without evidence of metastatic disease. This will be reviewed by UCLA neuroradiology to only include patients with high likelihood of GBM) Exclusion Criteria: 1. Pediatric patients 2. Diagnostic uncertainty (reviewed by UCLA neuroradiology history extracranial malignancy or autoimmune disease) 3. Medical conditions that make patients a poor candidate for anesthesia and/or surgery (decision for surgery will follow standard pre-operative clearance guidelines and will not differ for this specific study from standard of care treatment plan) 4. Involvement of eloquent areas (as defined by MRI signal clearly involving areas that would lead to a qualifying neurologic deficit as defined in surgical limiting toxicity - this will specifically include: 1) primary motor cortex, 2) primary sensory cortex, 3) sensorimotor fibers as defined on pre-operative diffusion tensor imaging, 4) primary language areas (Broca, Wernicke), 5) arcuate fasiculus as defined on pre-operative diffusion tensor imaging Pre-operative: Standard of care pre-operative MRI including perfusion and pH-weighted amine CEST-EPI (which will add up to 15 minutes of scan time) for a single pre-operative exam prior to surgery. Surgery: 1 day (subjects to be admitted to the hospital) Follow-up: inpatient stay (1-3 days), 2 week clinical assessment (outpatient post-op clinic visit). MRI and clinical assessment at 4 weeks (end of resection limited toxicity window). Following this, there will be standard of care follow up with MRI and clinical assessment starting at 8 weeks +/- 4 weeks (per RANO 2.0). 1 Total study duration for recruitment, enrollment, and study completion of all subjects is up to 2 years. Single-arm, surgical resection escalation safety trial with a preliminary efficacy study at the maximal tolerated resection This safety evaluation will mimic a phase 1 dose escalation safety study using a rule based approach on based on a i3+3 design.2 Using standard of care resection of contrast enhancement as the baseline, we will begin with 3 subjects with maximal resection + "CEST positive" areas 0.7 cm from the contrast enhancing boundary within areas of T2 hyperintensity. If there is not \> 1 pre-determined resection limiting toxicity (RLT, defined below) in this cohort, the r