Glioblastoma clinical trials — recruiting now

Combined chemoradiation and radiofrequency electromagnetic field treatment for patients with glioblastoma

The goal of this clinical trial is to evaluate the safety and feasibility of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption using the Next Generation Dome Helmet (NGDH) in adults with glioblastoma (GBM) undergoing the maintenance phase of the standard "Stupp protocol". Participants will: * Undergo repeated FUS BBB disruption treatments during the maintenance phase of temozolomide (TMZ) chemotherapy. * Receive intravenous ultrasound contrast (DEFINITY®) prior to each FUS session to facilitate targeted BBB disruption. * Undergo serial MRI scans and clinical assessments to evaluate safety and the extent of BBB opening. * Provide blood samples (and tumor tissue if available) for biomarker analysis related to BBB permeability, tumor presence, and treatment response. * Be followed for progression-free survival (PFS) and overall survival (OS) during routine neuro-oncology visits until end of life.

This phase I trial studies the side effects of nivolumab before and after surgery in treating children and young adults with high grade glioma that has come back (recurrent) or is increasing in scope or severity (progressive). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

The investigator propose a single-center randomized phase II controlled study designed to compare the management of first recurrence of GBM using etoposide versus tamoxifen.

Glioblastoma is the most aggressive primary brain tumor due to its highly infiltrative growth pattern, strong proliferative potential, and multiple mechanisms of resistance to treatment . Based on results from multicenter studies, English oncologist Roger Stupp proposed in 2005 a new treatment approach involving initial tumor resection followed by conformal external beam radiation therapy combined with temozolomide, plus subsequent cycles of monochemotherapy with this drug. This approach extended median survival by only 2 months, yet remains the standard of care due to lack of better alternatives. Consequently, recent protocols for malignant CNS tumors in Russia and internationally recommend prioritizing clinical trial enrollment over "standard" treatment. Numerous studies demonstrate that the extent of resection of contrast-enhancing GB volume on MRI positively correlates with progression-free and overall survival. This is explained by the fact that adjuvant chemoradiation methods and the body's immune responses show efficacy only with small residual tumor volumes. The interval between surgery and adjuvant therapy negatively correlates with survival outcomes, potentially because the mitotic cycle of GB stem cells lasts only 24 hours. From this perspective, intraoperative radiation therapy (IORT) may improve treatment results. Attempts to use various IORT technologies for malignant brain gliomas span several decades. Some studies reported better survival with IORT compared to controls, but most involved small patient groups without reliable resection control or dosimetric assessment due to technological limitations. Early IORT methods used bulky linear accelerators producing high-energy electron beams. With portable systems, renewed interest emerged first in breast cancer, then neurosurgery. Neuroimaging and software now enable precise treatment planning. Bensaleh S. et al. evaluated balloon brachytherapy (MammoSite®) for early breast cancer in 2009. The device featured a dual-lumen catheter with a balloon inserted into the resection cavity. After contrast inflation and CT planning, 192Ir delivered 34 Gy in 10 fractions over 5 days to 1 cm depth. While comparable to conventional radiotherapy in 3-5 year survival, the 16% infection rate from prolonged implantation was a major drawback. A case report described using a similar breast cancer system (Contura balloon applicator) for recurrent malignant glioma in a 47-year-old patient. A single 20 Gy fraction showed no complications at 6-month follow-up. The Zeiss INTRABEAM system uses a miniature 50 kV linear accelerator with rigid spherical applicators producing low-energy x-rays for high surface doses with limited penetration. The 2018 INTRAGO phase I/II trial by Giordano et al. evaluated dose escalation (20→40 Gy) in 15 newly diagnosed GB patients. No complications (wound healing issues, bleeding, ischemia, or radionecrosis requiring surgery) occurred. Median PFS was 17.7 months (95% CI 9.7-25.9) in protocol-compliant patients, with distant progression remaining challenging. A recent advancement is electronic brachytherapy using the Xoft Axxent eBx System, combining a 50 kV x-ray source with a silicone balloon applicator conforming to resection cavities. Initially successful in breast and gynecologic cancers, its application expanded to neuro-oncology. In 2016, the European Medical Center (EMC) initiated a pilot study using Axxent eBx for recurrent GB post-standard chemoradiation. Twenty-nine patients received 20 Gy to the balloon surface after maximal safe resection. Median OS was 28.7 months (range 14-104) from first surgery. In patients with ≤2.5 cm³ residual tumor (n=16), median local PFS was 14.5 months (8-94), with 6- and 12-month PFS rates of 68.9% and 31% respectively. One grade 3 radionecrosis case occurred (CTCAE), with no infections or CSF leaks. Study Rationale: * Demonstrated survival benefits with gross-total resection of contrast-enhancing tumor * Negative survival impact of delayed adjuvant therapy initiation * Promising preliminary results of resection plus electronic brachytherapy in recurrent GB from EMC research This is a pilot, prospective, single-center, non-comparative study. Patients (N=15) with newly diagnosed glioblastoma will undergo intraoperative balloon-based electronic brachytherapy (IOBT) using the Xoft® Axxent® eBx® System immediately following gross total resection of the contrast-enhancing tumor. A single fractional dose of 20 Gy will be delivered to the balloon surface. Subsequently, patients will receive standard chemoradiotherapy according to the Stupp protocol (2005): * Concurrent phase (initiated 2-4 weeks postoperatively): * Radiotherapy: Conformal external beam radiation therapy (EBRT) to a total dose of 60 Gy (2 Gy/fraction over 6 weeks). * Chemotherapy: Daily oral temozolomide (75 mg/m²) during EBRT. * Adjuvant phase: * Monotherapy: 6-12 cycles (6-12 months) of adjuvant temozolomide (150-200 mg/m², days 1-5 of each 2

ReciDOPA is a phase II, single-stage randomized, multicenter, prospective trial assessing the efficacy of an irradiation protocol based on Intensity-modulated radiation therapy with simultaneous-integrated boost guided by FDOPA-PET in patient with recurrent glioblastoma.

The researchers are doing this study to find out whether the radiopharmaceutical therapy (RPT) 177Lu-PSMA-617 is a safe treatment for people with IDH wild type glioma.

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.

The goal of this 1:1 randomized, multi-center, open-label phase Ib/II clinical trial is to explore the efficacy of the add-on of the anti-glutamatergic drugs gabapentin, sulfasalazine and memantine to standard chemoradiotherapy with temozolomide compared to chemoradiotherapy alone in patients with newly diagnosed glioblastoma.

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?

The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Different doses of Methimazole will be given to several study participants with glioblastoma. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the side effects occur that require the dose to be lowered. The procedures in this study are research blood draws, physical exams, collection of medical history, MRI scans, and study drug administration.

This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.

The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors.

The study seeks to assess the response of glioblastoma multiforme to treatment using weekly low field (0.35 T) MR-images of the brain at a MRIdian® linac system during standard radiotherapy at the same system. A total of 20 patients in a single arm will be recruited for this investigation. The imaging data will be used to evaluate the change in tumor volume over the course of the treatment and to perform radiomics in order to investigate the possibility of response prediction using these images. In order to assure sufficient image quality, prior to the main investigation, a group of up to 20 volunteers has MR scans taken with identical sequences to the main study phase.

This single center, single arm, open-label, phase I study will assess the safety of laparoscopically harvested autologous omentum, implanted into the resection cavity of recurrent glioblastoma multiforme (GBM) patients.

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T-cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat participants with cancers. They have shown promise, but have not been strong enough to cure most participants. The study team has found from previous research that we can put a new gene (a tiny part of what makes-up DNA and carries the participants traits) into T cells that will make them recognize cancer cells and kill them. In the lab, the study team has made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein found on the participants brain tumor. This CAR is called GPC3-CAR. To make this CAR more effective, the study has also added a gene that includes IL15. IL15 is a protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15. This study will test T cells with the IL15 GPC3-CAR (GO-CART T cells) in participants with GPC3-positive brain tumors. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The study team will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The study team will use this drug to kill the T cells if necessary due to side effects. This study will test T cells genetically engineered with a GPC3-CAR and IL15 (GO-CART T cells) in participants with GPC3-positive brain tumors. The GO-CART T cells are an investigational product not approved by the Food and Drug Administration.

This clinical trial aims to evaluate whether an oncolytic viral agent can treat recurrent glioblastoma. It will also assess the safety and tolerability of the oncolytic viral agent. The primary question it seeks to answer is: What medical problems do participants experience when injected with the oncolytic viral agent? Researchers will administer the oncolytic viral agent via intratumoral injection to determine its efficacy in treating recurrent glioblastoma. Participant Procedures: Receive the initial injection, followed by additional injections every 2-4 weeks for a total of 6 injections. Undergo physical examinations and tests every 2 to 4 weeks. Record their symptoms, hematological test results, and imaging findings.

The usual standard of care for patients over 65 diagnosed with glioblastoma ("GBM") or Grade 4 astrocytoma, IDH-mutant is a 3-week course of radiotherapy, with concurrent and adjuvant temozolomide (TMZ). This radiation dose and length of treatment are less than what would be given for younger patients, primarily due to unclear survival benefits from randomized trials. However, survival remains dismal, and may be partially due to the reduced radiation dose. Recent studies investigating this have found that increased radiation dose (to the equivalent of what is normally given over 6 weeks in younger patients) over 3 weeks is well-tolerated and has improved survival rates. Additionally, with the advent of novel technology such as the MR-Linac, adaptive radiotherapy with this regimen using reduced radiation margins is possible. Use of the MR-Linac allows for daily MRI scans to be done prior to treatment, so plans can be adapted to tumour dynamics and anatomical deformations. In this trial, we will examine the outcomes of increased radiation dose, combined with reduced-margin adaptive radiotherapy in this patient population.

This study is the first step in testing the hypothesis that adding Photobac® Photodynamic Therapy to surgical removal of a glioblastoma or gliosarcoma will be both safe and effective. Photodynamic Therapy (PDT) combines light and a photosensitizer. PDT has been used to treat a variety of cancers with varying degrees of success. For the past thirty years Photolitec has been working to develop a treatment for glioblastoma or gliosarcoma using light and a photosensitizer. Photolitec's scientists were looking for a photosensitizer that: 1. has no significant systemic toxicity apart from some temporary skin photosensitivity, 2. crosses the blood brain barrier, 3. accumulates to a high level in glioblastoma and minimally in the brain, 4. is activated by the wavelength of light that penetrates most deeply into the brain, 5. minimizes any temporary skin photosensitivity. Preliminary testing indicates the Photolitec team has achieved these five goals. Photolitec is now able to offer a clinical trial based on the results of this work.

There is no consensus on the optimal treatment of patients with high-grade glioma, especially when patients have limited functioning performance at presentation (KPS ≤70). Therefore, there are varied practice patterns around pursuing biopsy, resection, or palliation (best supportive care). This study aims to characterize the impact of palliative care versus biopsy versus resection on survival and quality of life in these patients. Also, it will aim to determine if there is a subset of patients that benefit the most from resection or biopsy, for which outcome, and how they could be identified preoperatively. This study is an international, multicenter, prospective, 3-arm cohort study of observational nature. Consecutive HGG patients will be treated with palliative care, biopsy, or resection at a 1:3:3 ratio. Primary endpoints are: 1) overall survival, and 2) quality of life at 6 weeks, 3 months and 6 months after initial presentation based on the EQ-5D, EORTC QLQ C30 and EORTC BN 20 questionnaires. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.