Ongoing Clinical Trials for Malignant Glioma
Malignant glioma is an aggressive brain tumor that affects both children and adults. Currently, there are 8 ongoing clinical trials investigating new treatment approaches for different types of this condition. These studies are testing novel medications and combination therapies across multiple European countries, with the goal of improving survival rates and treatment outcomes for patients with newly diagnosed or recurrent tumors.
Clinical trial locations
- Austria
- Belgium
- Czechia
- Denmark
- Study of ONC201 for Patients with Newly Diagnosed H3 K27M-mutant Diffuse Glioma After Radiotherapy
- Study of tovorafenib (DAY101) in children and young adults aged 6 months to 25 years with brain tumors and other solid tumors that have RAF gene changes
- Study of tovorafenib versus standard chemotherapy as first treatment for children with low-grade glioma with RAF gene changes
- Study Comparing Lomustine Alone and Lomustine with Bevacizumab for Patients with Recurrent Glioblastoma
- Finland
- France
- Study of Propranolol and Vinorelbine for Children and Teenagers with Refractory or Relapsing Solid Tumors
- Study of tovorafenib versus standard chemotherapy as first treatment for children with low-grade glioma with RAF gene changes
- Study on the Safety of Photodynamic Therapy with Aminolevulinic Acid Hydrochloride for Patients Aged 18-75 with Grade IV Glioblastoma
- Germany
- Study of ONC201 for Patients with Newly Diagnosed H3 K27M-mutant Diffuse Glioma After Radiotherapy
- Study of tovorafenib (DAY101) in children and young adults aged 6 months to 25 years with brain tumors and other solid tumors that have RAF gene changes
- Study of tovorafenib versus standard chemotherapy as first treatment for children with low-grade glioma with RAF gene changes
- Greece
- Hungary
- Ireland
- Italy
- Netherlands
- Study of ONC201 for Patients with Newly Diagnosed H3 K27M-mutant Diffuse Glioma After Radiotherapy
- Study of tovorafenib (DAY101) in children and young adults aged 6 months to 25 years with brain tumors and other solid tumors that have RAF gene changes
- Study of tovorafenib versus standard chemotherapy as first treatment for children with low-grade glioma with RAF gene changes
- Study on ONC201 and Paxalisib for Children and Young Adults with Diffuse Midline Gliomas, Including Diffuse Intrinsic Pontine Gliomas
- Norway
- Slovenia
- Spain
- Sweden
Study of ONC201 for Patients with Newly Diagnosed H3 K27M-mutant Diffuse Glioma After Radiotherapy
This trial is investigating ONC201, an oral medication, for patients with a specific type of brain tumor called H3 K27M-mutant diffuse glioma. The study focuses on patients who have recently completed radiation therapy as part of their initial treatment.
Main inclusion criteria: Participants must weigh at least 10 kg and have a confirmed diagnosis of H3 K27M-mutant diffuse glioma verified through certified laboratory testing. They must have completed standard radiotherapy within 2 to 6 weeks before joining the study, and this radiotherapy should have started within 12 weeks of initial diagnosis. At least one high-quality MRI scan must be available from before radiotherapy began. Participants need a performance status score of at least 70, indicating they can care for themselves and perform daily activities. If taking corticosteroids or anti-seizure medications, the dose must be stable or decreasing for 7 days before enrollment.
Main exclusion criteria: Patients who have not completed radiotherapy, those with brain tumor types other than H3 K27M-mutant diffuse glioma, and those unable to follow study procedures cannot participate. Pregnant or breastfeeding women are excluded, as are patients participating in other clinical trials simultaneously. Those with serious health conditions that might interfere with the study, recent surgeries affecting study results, allergies to the study medication, or a history of substance abuse are also excluded.
Trial focus: This is a double-blind, randomized study comparing ONC201 to placebo. The main goal is to evaluate whether ONC201 can improve overall survival and delay tumor progression after radiotherapy. Participants will be randomly assigned to receive either ONC201 capsules or placebo, with neither participants nor researchers knowing which group each patient is in. Regular assessments will monitor health status, side effects, and tumor response throughout the study period, which is expected to conclude in December 2026.
Investigational drug: ONC201 targets specific pathways in cancer cells that may help slow or stop tumor growth. It is administered orally and aims to improve outcomes for patients with this aggressive form of brain tumor.
Study of Propranolol and Vinorelbine for Children and Teenagers with Refractory or Relapsing Solid Tumors
This French trial is testing a combination of propranolol and vinorelbine for children and teenagers with solid tumors that have not responded to previous treatments or have returned after treatment.
Main inclusion criteria: Participants must be between 4 and 24 years old with confirmed refractory or relapsing solid tumors for which no effective standard treatment exists. The disease must have measurable tumors according to specific medical criteria. Patients must have a performance score greater than 50, indicating they can perform daily activities. Adequate blood counts are required, including sufficient white blood cells, neutrophils, and platelets. Normal kidney and liver function within specified ranges is necessary. Participants must be able to swallow softgel capsules or liquid medicine, have a life expectancy of more than 3 months, and be part of a social security program.
Main exclusion criteria: Patients unable to take oral medications three times weekly or daily as required are excluded. Those unwilling to follow study procedures, with interfering medical conditions, who are pregnant or breastfeeding, or participating in another clinical trial cannot join. Known allergies to navelbine or propranolol also prevent participation.
Trial focus: The study aims to determine the highest dose of vinorelbine that can be safely tolerated when combined with daily propranolol. Vinorelbine is taken three times weekly, while propranolol is administered daily. The trial monitors how well participants tolerate the treatment and assesses effectiveness in controlling cancer over six months. The initial treatment cycle lasts 56 days, after which further treatment decisions are made based on response and tolerance.
Investigational drugs: Propranolol, commonly used for heart conditions, is being explored for potential cancer treatment benefits. Vinorelbine is a chemotherapy drug that slows cancer cell growth by disrupting cell division.
Study of tovorafenib (DAY101) in children and young adults aged 6 months to 25 years with brain tumors and other solid tumors that have RAF gene changes
This trial investigates tovorafenib, also known as DAY101, for young patients with low-grade brain tumors and other solid tumors that have specific RAF gene alterations.
Main inclusion criteria: Patients must be between 6 months and 25 years old with confirmed low-grade glioma or advanced solid tumor showing RAF alterations. For low-grade glioma patients, there must be evidence of tumor progression after at least one previous treatment. At least one tumor must be measurable or evaluable by medical imaging. Participants need a performance score of at least 50 on either the Karnofsky scale (for those 16 and older) or Lansky scale (for those under 16). Cancer must be confirmed through tissue examination at initial diagnosis or recurrence.
Main exclusion criteria: Patients younger than 6 months or older than 25 years, those without RAF gene alterations, and those with no evidence of tumor progression or recurrence cannot participate. Previous treatment with tovorafenib, inability to take oral medications, presence of serious medical conditions that could interfere with participation, current participation in other trials, pregnancy or breastfeeding, and known allergies to the study medication or its components are all exclusion factors.
Trial focus: Participants are assigned to one of three treatment groups based on their specific genetic changes. The medication comes in two forms: powder that can be mixed into liquid or tablets. Regular monitoring tracks tumor size using imaging scans and records any side effects. The study measures how well tovorafenib works in treating these tumors and aims to understand its safety profile. Treatment may continue for up to 72 months depending on individual response.
Investigational drug: Tovorafenib is an oral pan-RAF inhibitor that targets and blocks RAF proteins involved in cancer cell growth. It specifically addresses tumors with BRAF alterations or RAF fusions, interfering with abnormal cell signaling that causes tumor growth.
Study of tovorafenib versus standard chemotherapy as first treatment for children with low-grade glioma with RAF gene changes
This large multinational trial compares tovorafenib with standard chemotherapy as first-line treatment for pediatric low-grade brain tumors with RAF gene alterations.
Main inclusion criteria: Participants must be under 25 years old with confirmed low-grade glioma or glioneuronal tumor containing activating RAF alterations. The diagnosis must be confirmed through tissue examination. At least one measurable tumor must be present on imaging tests. Patients must be starting systemic therapy for the first time, meaning they have not previously received medication that travels through the bloodstream to treat the tumor.
Main exclusion criteria: Patients without confirmed pediatric low-grade glioma diagnosis or without RAF alterations in their tumor cannot participate. Those who have already received systemic therapy, patients younger than 6 months or older than 25 years, those with previous tovorafenib treatment, and those with severe heart, liver, or kidney problems are excluded. Pregnant or breastfeeding patients, those in other clinical trials, patients unable to undergo required medical tests, those with known allergies to study medications, patients with major surgery within 4 weeks before the study, and those unable to swallow oral medications cannot join.
Trial focus: Participants are randomly assigned to receive either tovorafenib (taken orally as tablets or suspension) or standard chemotherapy (vincristine, vinblastine, and carboplatin given through an IV line). Regular imaging scans measure tumor response, and the study tracks how long patients remain free from tumor growth. The trial continues until March 2030, monitoring both treatment effectiveness and overall health status over the long term.
Investigational drugs: Tovorafenib is a targeted therapy that blocks specific molecular pathways involved in tumor growth, particularly the RAF signaling pathway. Standard chemotherapy includes established cancer-fighting medications proven effective for this type of brain tumor.
Study on Bortezomib and Temozolomide for Patients with Recurrent Grade IV Glioma
This Norwegian trial examines the combination of bortezomib and temozolomide for patients whose Grade IV glioma has returned after treatment.
Main inclusion criteria: Patients must be 18 years or older with confirmed recurrent Grade IV glioma shown by MRI within 14 days before enrollment. The tumor must have returned at least 12 weeks after completing radiation therapy and must be measurable. A Karnofsky performance status of 70% or higher is required, meaning patients can care for themselves and perform normal activities. Adequate blood counts are necessary, including white blood cells at least 3,000 per cubic millimeter, neutrophils at least 1,500 per cubic millimeter, platelets at least 100,000 per cubic millimeter, and hemoglobin at least 10 grams per deciliter. Normal liver function and kidney function (GFR at least 60) are required. The tumor must have an unmethylated MGMT promoter genetic feature. Patients must be eligible for standard temozolomide treatment and provide tumor tissue samples.
Main exclusion criteria: Patients with brain tumor types other than Grade IV glioma, those not within the specified age range, and vulnerable populations requiring special protection cannot participate. Patients who have been pre-treated with bortezomib before combining it with temozolomide are also excluded.
Trial focus: The study has two phases. Phase IB assesses the safety and tolerability of combining bortezomib and temozolomide, determining the optimal dosage. Bortezomib is given as an intravenous injection while temozolomide is taken orally. Phase II evaluates treatment effectiveness, measuring progression-free survival and overall survival rates. Regular monitoring includes blood tests and neurological exams every four weeks, with MRI scans every 12 weeks. The trial involves 63 patients total and aims to provide insights into whether this combination offers benefits for recurrent Grade IV glioma.
Investigational drugs: Bortezomib is a proteasome inhibitor that may make cancer cells more sensitive to treatment. Temozolomide is a chemotherapy drug that damages cancer cell DNA, preventing cell division and growth.
Study on the Safety of Photodynamic Therapy with Aminolevulinic Acid Hydrochloride for Patients Aged 18-75 with Grade IV Glioblastoma
This French trial investigates photodynamic therapy using Pentalafen combined with a specialized light device during surgery for newly diagnosed glioblastoma patients.
Main inclusion criteria: Participants must be males or females between 18 and 75 years old with newly diagnosed glioblastoma suspected based on clinical examination and MRI results. A Karnofsky Performance Score of 70 or higher is required. Patients must be eligible for surgery with maximum possible tumor removal based on MRI results. They must be planning to receive standard Stupp Protocol treatment after surgery and be able to take oral medications. The tumor must be suitable for photodynamic therapy as confirmed by the study doctor and sponsor based on pre-surgery MRI data.
Main exclusion criteria: Patients with brain tumor types other than high-grade glioma or glioblastoma, those outside the specified age range, and vulnerable populations unable to give consent cannot participate.
Trial focus: During surgery, photodynamic therapy is applied using the Heliance device in combination with Pentalafen medication taken orally as a powder. The study monitors treatment safety, tolerability, and determines the optimal light dose for future trials. Researchers also assess time to disease progression and gather feedback on device usability. After surgery, participants continue with standard glioblastoma care and undergo regular follow-up assessments to monitor health and treatment effects.
Investigational drugs: Pentalafen contains aminolevulinic acid hydrochloride, a photosensitizer that accumulates in cancer cells. When activated by light from the Heliance device during photodynamic therapy, it produces oxygen that destroys cancer cells.
Study Comparing Lomustine Alone and Lomustine with Bevacizumab for Patients with Recurrent Glioblastoma
This Danish trial compares lomustine alone versus lomustine combined with bevacizumab for patients with recurrent glioblastoma.
Main inclusion criteria: Participants must have confirmed glioblastoma that has returned after treatment with the STUPP regimen. They must be older than 18 years with a Performance Status of 0-1, meaning they are fully active or have some symptoms but can still do light work. Expected survival must be more than 3 months. The cancer should have progressed for the first time after radiation therapy and chemotherapy, with progression occurring at least 3 months after finishing radiotherapy and at least 4 weeks after finishing chemotherapy. Patients should not have had more than one type of chemotherapy treatment, including temozolomide.
Main exclusion criteria: Patients with serious medical conditions that could interfere with the study, those unable to follow study procedures, recent participants in other clinical trials, pregnant or breastfeeding women, and those with allergic reactions to study medications are excluded. Patients who have not recovered from recent surgery, those with certain infections, patients taking interfering medications, and those with substance abuse history or mental health conditions affecting participation cannot join.
Trial focus: Participants are randomly assigned to receive either lomustine alone or lomustine combined with bevacizumab. Lomustine is taken orally as a capsule, while bevacizumab is administered as an intravenous infusion. The study monitors overall survival, progression-free survival at 6 and 12 months, response rate, and duration of response. Regular assessments track treatment effectiveness and any side effects. The trial is estimated to conclude by December 2026.
Investigational drugs: Lomustine is a chemotherapy drug that interferes with cancer cell DNA, preventing cell division. Bevacizumab is a monoclonal antibody that prevents the growth of new blood vessels that tumors need to grow.
Study on ONC201 and Paxalisib for Children and Young Adults with Diffuse Midline Gliomas, Including Diffuse Intrinsic Pontine Gliomas
This Netherlands-based trial tests the combination of ONC201 and paxalisib for children and young adults with diffuse midline gliomas, including the particularly aggressive diffuse intrinsic pontine gliomas.
Main inclusion criteria: Participants must be between 2 and 39 years old with new diagnosis of diffuse midline glioma confirmed by imaging or tissue tests. For certain groups, patients must have completed radiation therapy and be within 4-14 weeks of finishing this therapy. Some groups require evidence of tumor progression with no treatment received for this progression. Participants must have used temozolomide or dexamethasone during radiation therapy and have stable or decreasing doses of dexamethasone for at least 3 days before baseline MRI. Adequate organ function is required, including healthy bone marrow, kidneys, liver, lungs, stomach, metabolism, and heart. A performance score of at least 50 is necessary. Participants must weigh at least 10 kg and be willing to provide tumor tissue samples.
Main exclusion criteria: Patients without diffuse midline glioma diagnosis, those outside the specified age range, and those unable to follow study procedures or take medications as required cannot participate. Pregnant or breastfeeding patients, those in other clinical trials, patients with recent treatments that might affect study results, those with allergies to study medications, and those with interfering medical conditions are excluded.
Trial focus: Participants are assigned to cohorts based on their condition and treatment history. Both ONC201 and paxalisib are administered orally in capsule form, with specific dosage and frequency determined by study protocol and assigned cohort. The study measures progression-free survival at 6 months for certain cohorts and overall survival at 7 months for others. Regular monitoring includes imaging tests, blood tests, and other evaluations to assess treatment response and side effects. The study continues until January 2026.
Investigational drugs: ONC201 blocks certain receptors in the brain and is being studied in combination with paxalisib, which inhibits specific enzymes involved in tumor growth. The combination aims to improve survival outcomes for these aggressive brain tumors.
Summary
These eight ongoing clinical trials represent important research efforts to improve treatment options for various forms of malignant glioma. The trials span multiple European countries, with notable concentration in the Netherlands, Denmark, Germany, and France. Several studies focus specifically on pediatric populations, reflecting the particular challenge these aggressive brain tumors pose for children and young adults.
A clear trend emerges around targeted therapies, particularly medications addressing RAF gene alterations. Tovorafenib appears in multiple trials, being tested both against standard chemotherapy and as a treatment for recurrent disease. ONC201 is also featured in several studies, either alone or in combination with other agents, targeting specific genetic mutations in these tumors.
The trials address different stages of treatment, from newly diagnosed cases to recurrent disease, and explore various approaches including targeted molecular therapies, combination chemotherapy, and innovative techniques like photodynamic therapy during surgery. This diversity of approaches reflects the complexity of treating malignant glioma and the ongoing search for more effective treatment strategies.
