Clinical Research Directory

Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma

Preclinical data have demonstrated the combination of azeliragon, a RAGE inhibitor, with radiation therapy (RT) can effectively reduce immune-suppressive myeloid cells and restore T-cell activation to improve tumor control in murine glioma models. Ongoing clinical studies of azeliragon with RT alone and RT plus temozolomide (TMZ) to treat patients with newly diagnosed glioblastoma (GBM) have demonstrated safety and tolerability. The purpose of this window-of-opportunity study is to validate that the combination of azeliragon with RT and TMZ would modulate immune-suppressive myeloid and T cells in the tumor microenvironment in patients with GBM.

Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care

This is a Phase 3 prospective, randomized, superiority, open-label, multi-site study. The overview of this study is as follows: * A Screening/Baseline Period of 21 days. During this time, patients will be randomized into a 1:2 allocation of Arm A:Arm B. * A Perioperative/Operative Phase where patients will undergo tumor resection (Arm A) or tumor resection plus GammaTile implantation (Arm B). * An EBRT Prior to Start Period. This occurs within 10 business days prior to EBRT and Concurrent TMZ Phase. * An EBRT and Concurrent TMZ Phase, which will begin 30 ±10 days post-surgery. EBRT (30 fractions) and TMZ will be administered up to 5 days a week for 6 weeks in Arm A, and EBRT (20 fractions) and TMZ will be administered for up to 5 days a week for 4 weeks in Arm B. TMZ will be administered at a dose of 75 mg/m2/day orally for each Arm. * An Adjuvant TMZ Phase, which begins 28 ±7 days following the EBRT and Concurrent TMZ Phase, and is comprised of six 28-day cycles. TMZ (150-200 mg/m2/day orally) will be administered for the first 5 days of each 28-day cycle for each Arm. Tumor treating fields are allowed but are not mandated during this phase. Up to 6 additional cycles (for a total of 12) can be completed at the discretion of the Investigator. * An Early Discontinuation/Follow-Up Phase will occur 28 ±7 days after completion of Cycle 6 of the Adjuvant TMZ Phase, regardless of the total number of cycles completed or any delays in cycle start. If fewer than six cycles are completed, the first follow-up assessment will occur 28 ±7 days after the last administered dose of adjuvant TMZ. If patient has a qualifying event requiring entrance to Early Discontinuation Phase, the first follow-up assessment will occur as soon as feasible, but within 28 days. For any unscheduled visits, data collected should be documented in the case report form (CRF) and must include, but are not limited to, safety evaluations, survival status, and disease status.

Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma

This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients with newly diagnosed glioblastoma receiving concurrent radiation and temozolomide.

Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant

The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K/mTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant. The main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG/DIPG or DHG H3G34-mutant.

Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations

This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Poly adenosine diphosphate (ADP) ribose polymerases (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.

IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma

This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in CD70+ adult glioblastoma

Glioblastoma Radiotherapy Using IMRT or Proton Beams

Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter. The aim of the GRIPS study is to prospectively test this clinical benefit in a randomized, open-label Phase III study. Patients are treated in the study using either modern photon radiation techniques (standard arm) or proton beams (experimental arm). The primary endpoint is the cumulative toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

DC Migration Study to Evaluate TReg Depletion In GBM Patients With and Without Varlilumab

Patients with newly diagnosed glioblastoma will be consented following tumor resection then undergo leukapheresis for harvest of peripheral blood leukocytes for generation of dendritic cells. Subjects will then receive standard of care (planned 6 weeks) radiation therapy (RT) and concurrent temozolomide (TMZ) at a standard targeted dose of 75 mg/m2/day. The study cycle of TMZ comprises a targeted dose of 150-200mg/m2/day for 5 days every 4 (+2) weeks for up to 12 cycles (patients with unmethylated MGMT gene promoter will receive only cycle 1). All patients will receive up to a total of 10 DC vaccines called pp65 CMV dendritic cells (DC). Dendritic Cell (DC) vaccines #1-3 will be given every two weeks, thus delaying the initiation of TMZ cycle 2 for patients receiving TMZ. All remaining TMZ/vaccine cycles will be 4 (+2) weeks in length. After the first 3 DC vaccines given during Cycle 1 of TMZ, the remaining DC vaccine injections are given on Day 21 (+/- 2 days) of each TMZ cycle. Subjects with unmethylated MGMT will only receive one cycle of adjuvant TMZ; however, their vaccine schedule will follow the same 4 (+ 2) week TMZ cycle schedule. Following RT, patients will be randomized into 1 of 3 groups. Groups 1 and 2 will be blinded. The groups differ in the type of pre-conditioning received prior to DC vaccine #4; additionally, Group 3 will be receiving infusions of varlilumab 7 days prior to and with vaccine #1 and 7 days prior to vaccine #3+. The pre-conditioning for each group is as follows: Group 1: Unpulsed DC pre-conditioning prior to DC vaccine #4; Group 2: Tetanus-diphtheria (Td) pre-conditioning prior to DC vaccine #4; Group 3: Td pre-conditioning prior to DC vaccine #4 and varlilumab infusion at 7 days prior to each DC vaccine (except DC vaccine #2) with Td pre-conditioning prior to vaccine #4.

Analysis of Cerebrospinal Fluid Leakage After Surgery for Intracranial Tumors

Cerebrospinal fluid is a clear fluid that surrounds and protects the brain. During surgery for brain tumors, neurosurgeons often need to open the covering of the brain (the dura) to reach the tumor. At the end of the operation, this covering is carefully closed again. In some cases, the closure might not be completely adequate leading to cerebrospinal fluid leak. This leakage may collect under the scalp or flow out through the surgical wound. When this happens, the surgical wound may not heal properly, and the risk of infection can increase. These complications can delay recovery and may postpone additional treatments, such as radiotherapy or chemotherapy, that are often needed after brain tumor surgery. Although cerebrospinal fluid leakage is less common after supratentorial craniotomy (surgery on the upper part of the brain) than after other types of brain surgery, it remains a challenging complication and has not been well studied in this group of patients. The aim of this study is to determine how often cerebrospinal fluid leakage occurs after supratentorial craniotomy for intracranial tumors, identify factors that increase the risk of leakage, and evaluate how these leaks are managed. Understanding these factors may help reduce the occurrence of cerebrospinal fluid leakage and improve postoperative recovery in the future.

A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.

A Dose Finding Study of \[177Lu\]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent

Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma

This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.

Comparison of Skin Closure Techniques in Oncological Neurosurgical Procedures: Intradermal Running Suture Versus Transdermal Interrupted Sutures

The purpose of this study is to compare two commonly used methods of closing the skin after surgery for an intracranial tumor. Skin closure is one of the most important steps in neurosurgical procedures, as it has a major influence on how well the wound heals. In patients with brain tumors, proper wound healing is especially important because it may affect how soon additional treatments, such as radiotherapy or chemotherapy, can be started. There are different ways to close the skin after surgery, including running sutures and interrupted sutures. Both methods are widely used and considered safe. However, in oncological neurosurgery, there is limited scientific evidence comparing their effects, and the choice of technique is often based on the surgeon's personal experience. In this study, investigators will compare skin closure using running absorbable sutures with interrupted non-absorbable sutures. Investigators will evaluate how well, depending on used suturing methods, the wound heals and how often wound-related complications occur, such as infection, separation of the wound edges, or leakage of cerebrospinal fluid. Investigators believe that the results of this study will help improve wound care in patients undergoing neurosurgical treatment for brain tumors and, as a result, may contribute to better recovery and overall quality of life.

Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma

This phase III trial compares the effect of adding lomustine to standard chemotherapy with temozolomide and radiation therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly diagnosed MGMT methylated glioblastoma. MGMT methylated tumors are more likely to respond to temozolomide chemotherapy. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's DNA and may kill tumor cells. Radiation therapy uses high energy x-ray photons to kill tumor cells and shrink tumors. Adding lomustine to standard chemotherapy with temozolomide and radiation therapy may shrink or stabilize glioblastoma.

Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma

Glioblastoma is the most aggressive brain tumor and often recurs locally despite intensive treatment. Standard chemoradiotherapy with 60 Gy may not be sufficient to control the tumor, and dose escalation seems to be warranted, but causes more toxicity. To address this, the multicentric PRIDE trial employs two cycles of bevacizumab to achieve dose escalation isotoxically. The goal is improved survival without significantly increasing side effects. The study uses a simultaneous integrated boost with a total dose of 75 Gy in 2.5 Gy per fraction.

The Cancer Connected Access and Remote Expertise Beyond Walls Program to Provide In-Home Cancer Treatment and Improve Treatment Satisfaction in Cancer Patients Living in the Florida Panhandle and Surrounding Areas

This phase II trial studies whether providing cancer treatment in the home is preferred over the traditional clinic setting and if it improves treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas. Typically, drug-related cancer care is provided at a medical center which causes patients to have to spend considerable time away from their family, friends, and familiar surroundings. This may add to the physical, emotional, social, and financial burden for patients and their families during this difficult time in their lives. The Cancer Connected Access and Remote Expertise (CARE) Beyond Walls (CCBW) program uses a specialized care team trained to provide cancer treatment in the patient's home setting. It is designed to support remote connection between the home health team and providers and Mayo clinic. This may be preferred over the traditional clinic setting which may improve treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas.

A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma

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. All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\*).

Safety and Efficacy of CTX-009 With or Without CTX-471 for Recurrent Glioblastoma

This is a phase IB/II, open-label study evaluating CTX-009 as monotherapy and in combination with CTX-471. The study evaluates the safety and efficacy of the monotherapy and the combination in patients with recurrent glioblastoma. The study tests the hypothesis that treatment with CTX-009 alone or in combination with CTX-471 will lead to enhanced tumor control and prolongation of overall survival of patients with recurrent glioblastoma. CTX-009 expands on existing anti-angiogenic therapies by ablating key compensatory and resistance mechanisms to bevacizumab, CTX-471 restores local immune reactivity through activation of costimulatory immune mediators. Combination of these two agents may further impair tumor proliferation through synergistic effects on the tumor microenvironment

Sonobiopsy for Noninvasive and Sensitive Detection of Glioblastoma

This clinical study to evaluate sonobiopsy is significant because sonobiopsy will fundamentally enhance the clinician's insight into the molecular features of an intracranial lesion to tailor treatment approaches and optimize outcomes. In addition to the standard diagnostics of anatomic imaging and surgical histology, sonobiopsy has the potential to become the third pillar for brain tumor management by radically advancing the ability to easily and regularly acquire tumor genetic and molecular signatures. This enhanced capability will have a dramatic impact on patient survival and quality of life.

Study of ABBV-637 or ABBV-155 With ERAS-801 for People With Glioblastoma

The researchers are doing this study to find out whether the drugs ABBV-637 and ABBV-155 are safe treatments that cause few or mild side effects when given alone or in combination with ERAS-801 in people with recurrent GBM.

A Study to Test a New Fluid to Improve the Quality of Images Obtained by Using Sound Waves (Ultrasound) During Surgery

The objective of this clinical investigation is to assess the safety and performance of the SonoClear® System. Performance will be assessed by analysis of the contrast-to-noise ratio (CNR) and assessment of image quality by using the Surgeon Image Rating (SIR) Scale. This is a prospective, multi-centre single arm study where the performance of the SonoClear® System relative to routinely used acoustic coupling fluid is investigated by each patient being their own control. Patients with the diagnosis of high-grade glioma (HGG) and low-grade glioma (LGG) at up to 5 sites in Germany will be included. Additionally, safety data are collected at 72 hours, 30 days and 6 months post procedure.

Study of Pamiparib in Newly Diagnosed and rGBM

This is an open-label, single-center Phase 0/2 study that will enroll up to 30 participants with newly diagnosed (N=12) and recurrent glioblastoma (N=18). The trial will be composed of a Phase 0 component (subdivided into Arm A, Arm B, and Arm C), and an Exploratory Phase 2 component. Participants with tumors demonstrating a PK response in the Phase 0 component of the study will graduate to an exploratory Phase 2 component that combines therapeutic dosing of pamiparib plus fractionated radiotherapy (for unmethylated MGMT promoter newly-diagnosed cases), pamiparib plus fractionated radiotherapy (for recurrent cases) or Olaparib plus fractionated radiotherapy (recurrent cases).

Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

This is a single-center, open-label, dose-escalating Phase 0 trial that will enroll participants with a confirmed diagnosed recurrent high-grade glioma (grade 3 or 4 per WHO criteria) targeting the mTOR pathway. Eligible participants will be administered a single infusion of temsirolimus through super-selective intra-arterial infusion or intravenous infusion. Participants will receive the study drug administration on the same day as the planned surgical resection of the tumor.

PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications

Background: About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers. Objective: To test a study drug (PLX038) in people with tumors of the brain or spinal cord. Eligibility: People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor. PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home. Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy. Study treatment will continue up to 7 months. Follow-up visits will continue every few months for up to 5 years.