Ongoing Clinical Trials for Brain Stem Glioma
Brain stem glioma, including diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas, is a rare and aggressive type of brain tumor that primarily affects children, adolescents, and young adults. Currently, there are 5 ongoing clinical trials testing various treatment combinations, including novel medications such as ONC201, everolimus, paxalisib, sirolimus, trametinib, nimotuzumab, vinorelbine, and experimental cell therapies. These trials are being conducted across several European countries, focusing on improving survival and quality of life for patients with these challenging brain tumors.
Clinical trial locations
- Denmark
- France
- Italy
- Netherlands
- Poland
- Spain
- Study on ONC201 and Everolimus with Radiotherapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Other Diffuse Midline Gliomas in Children, Adolescents, and Adults
- Study on the Safety and Efficacy of AloCelyvir for Children, Adolescents, and Young Adults with Diffuse Intrinsic Pontine Glioma or Medulloblastoma.
- Sweden
Study on ONC201 and Everolimus with Radiotherapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Other Diffuse Midline Gliomas in Children, Adolescents, and Adults
This international trial is testing two different treatment approaches for newly diagnosed DIPG and other diffuse midline gliomas with specific genetic changes (H3K28M mutation or EZHIP positive). The study compares ONC201 against everolimus, both combined with radiotherapy.
Main inclusion criteria: Patients must have a confirmed diagnosis of DIPG or diffuse midline glioma through clinical, radiological, or tissue examination methods. The tumor must show specific genetic markers (H3K28M mutation or EZHIP positive). Participants can be children over 6 months old, adolescents, or adults, with no upper age limit. They must have a life expectancy of more than 12 weeks and adequate organ function, including healthy bone marrow, kidneys, and liver. No prior chemotherapy or radiation therapy for the current cancer is allowed, though surgery for diagnosis is permitted.
Main exclusion criteria: Patients who have already received chemotherapy or brain radiation for their current tumor cannot participate. Those with other medical conditions that might interfere with the study treatments or affect their safety are excluded. Patients unable to follow study procedures or attend required visits are not eligible.
Focus and goal: The trial aims to evaluate progression-free survival, meaning how long patients live without their disease getting worse. Participants are randomly assigned to receive either ONC201 or everolimus, both taken orally as capsules or tablets, alongside radiotherapy. The study monitors treatment safety, side effects, and effectiveness through regular follow-up appointments including physical exams, imaging tests, and laboratory tests. This research will help determine the best treatment options for these aggressive brain tumors.
Investigational drugs: ONC201 (also called Dordaviprone) targets specific pathways in cancer cells that may help stop tumor growth. Everolimus blocks a protein that helps cancer cells grow and divide, and is already used to treat some types of cancer. Both medications are being tested to see if they can improve outcomes when combined with radiotherapy.
Study on ONC201 and Paxalisib for Children and Young Adults with Diffuse Midline Gliomas, Including Diffuse Intrinsic Pontine Gliomas
This Dutch trial tests the combination of ONC201 and paxalisib for children and young adults with diffuse midline gliomas at different stages of treatment, including newly diagnosed patients, those who have completed radiation therapy, and those whose tumors have returned.
Main inclusion criteria: Patients must be between 2 and 39 years old with a confirmed diagnosis of diffuse midline glioma. Depending on the study group, participants must have either newly diagnosed disease, completed radiation therapy within 4-14 weeks, or have tumor progression without recent treatment. Patients must have used temozolomide or dexamethasone during radiation therapy and have stable doses of dexamethasone for at least 3 days before baseline scans. Adequate organ function is required, including healthy bone marrow, kidneys, liver, and heart. Participants must weigh at least 10 kg and have recovered from side effects of any previous treatments.
Main exclusion criteria: Patients without a confirmed diagnosis of diffuse midline gliomas cannot participate. Those outside the specified age range (2-39 years) are excluded. Pregnant or breastfeeding patients cannot join. Those currently participating in another clinical trial or who have received certain recent treatments are not eligible. Patients with allergies to the study medications or with other medical conditions that might interfere with the study are excluded.
Focus and goal: The study evaluates progression-free survival at 6 months for newly diagnosed and post-radiation patients, and overall survival at 7 months for those with recurring tumors. Both medications are taken orally as capsules. The trial monitors treatment response through regular assessments including imaging tests and blood work to determine if this combination can slow disease progression or improve survival rates.
Investigational drugs: ONC201 is a small molecule that blocks specific receptors in the brain and targets pathways that promote cancer cell death. Paxalisib inhibits specific enzymes involved in tumor growth. Both are being tested together to see if their combined effect can improve outcomes for patients with these challenging brain tumors.
Study on the Effectiveness of Sirolimus and Trametinib for Treating Diffuse Intrinsic Pontine Glioma in Children Aged 3-18 Years
This Polish trial focuses on personalized treatment for children with DIPG by using molecular testing to identify specific markers in the tumor and then selecting the most appropriate medication based on these findings.
Main inclusion criteria: Children must be between 3 and 18 years old with a diagnosis of DIPG confirmed by both symptoms and imaging tests like MRI. A tissue sample must show glioma classified as WHO grade III or IV, confirmed by a specialist pathologist. Parents or legal guardians must sign an informed consent form, and patients over 13 years old must also provide consent. The consent covers all study procedures, including special genetic tests using next-generation sequencing (NGS).
Main exclusion criteria: Patients without a confirmed DIPG diagnosis cannot participate. Those outside the 3-18 age range are excluded. Patients who cannot safely undergo the study treatments or cannot comply with study procedures and follow-up requirements are not eligible.
Focus and goal: The study uses molecular profiling to identify important markers that guide treatment selection. Sirolimus is given during radiotherapy as an oral solution or tablets, followed by the addition of trametinib in tablet form after radiotherapy ends. The primary goal is to measure overall survival from diagnosis. The study also assesses safety, monitors disease progression through MRI scans every 2 months, and evaluates quality of life using a pediatric quality of life inventory. This personalized approach aims to develop optimal treatment plans based on each child’s unique tumor characteristics.
Investigational drugs: Sirolimus is an immunosuppressant that targets specific molecular markers by inhibiting a protein called mTOR, which plays a role in cell growth. Trametinib blocks MEK1 and MEK2 proteins, which are part of a pathway controlling cell division and survival. Both medications are being tested for their ability to target specific molecular characteristics identified in each patient’s tumor.
Study on Radiotherapy with Nimotuzumab and Vinorelbine for Newly Diagnosed Childhood and Adolescent Diffuse Intrinsic Pontine Glioma (DIPG) Patients
This Italian trial compares different radiotherapy approaches combined with two medications, nimotuzumab and vinorelbine, for newly diagnosed DIPG in children and adolescents.
Main inclusion criteria: Patients must be between 2 and 21 years old with newly diagnosed DIPG confirmed by MRI characteristics in the pons area of the brain. Symptoms must have been present for less than 6 months. No previous treatments are allowed except for steroids. Patients must have a life expectancy of at least 4 weeks and a performance status of 40% or higher on the Karnofsky/Lansky scale, which measures ability to perform daily activities. Adequate organ function is required with no significant dysfunction. A baseline brain MRI with contrast agent and a spinal MRI are mandatory. Written informed consent must be obtained from parents or legal guardians before starting treatment.
Main exclusion criteria: Patients with brain tumors other than DIPG cannot participate. Those outside the specified age range or who cannot follow study procedures are excluded. Pregnant or breastfeeding patients are not eligible. Those currently participating in another clinical trial or who have had certain recent treatments are excluded. Patients with other serious health conditions that might interfere with the study cannot participate.
Focus and goal: The study compares conventional radiotherapy versus experimental radiotherapy approaches, both combined with nimotuzumab and vinorelbine given intravenously. The primary aim is to evaluate the best tumor response up to 36 weeks. The trial also monitors time until disease progression, tumor recurrence, development of new cancers, and overall survival. Regular MRI scans track tumor response, and in cases of relapse, re-irradiation may be considered.
Investigational drugs: Nimotuzumab is a monoclonal antibody that targets specific proteins on cancer cells called epidermal growth factor receptor (EGFR), which may help slow tumor growth. Vinorelbine is a chemotherapy drug that interferes with cell division by disrupting microtubules, thereby inhibiting cancer cell growth. Both medications are given as intravenous infusions alongside radiotherapy.
Study on the Safety and Efficacy of AloCelyvir for Children, Adolescents, and Young Adults with Diffuse Intrinsic Pontine Glioma or Medulloblastoma
This Spanish trial tests an innovative cell-based therapy called AloCelyvir for both newly diagnosed DIPG and relapsed or worsening medulloblastoma, another type of brain tumor.
Main inclusion criteria: Patients must be between 1 and 21 years old. For newly diagnosed DIPG, patients should not have received previous radiotherapy or chemotherapy and must be able to receive radiotherapy. The diagnosis can be clinical, radiological, or confirmed by tissue examination. For medulloblastoma that has returned or worsened, patients must have already tried surgery, radiation therapy, and chemotherapy without success. Patients must have recovered from previous treatment side effects to a mild level, except for hearing loss, hair loss, and nerve damage. A performance status of at least 50% is required. Adequate organ function is necessary, including specific levels of blood cells, kidney function, and liver function. The disease must be measurable according to medical criteria. Patients must have a life expectancy of at least 8 weeks and be able to comply with the treatment schedule.
Main exclusion criteria: Patients without confirmed DIPG or worsening medulloblastoma cannot participate. Those outside the specified age range (1-21 years) are excluded. Patients who cannot safely receive AloCelyvir, either alone or combined with radiotherapy, are not eligible. Pregnant patients and those unable to use effective contraception are excluded.
Focus and goal: The study evaluates the safety and effectiveness of AloCelyvir, which combines special mesenchymal cells from bone marrow with a modified virus called ICOVIR-5. For newly diagnosed DIPG, AloCelyvir is tested in combination with radiotherapy. For relapsed medulloblastoma, it is tested as a standalone treatment. The medication is given through intravenous infusion. Regular visits monitor health status, treatment response, and any side effects. The trial aims to understand how well this cell-based therapy works and ensure its safety for young patients with these aggressive brain tumors.
Investigational drugs: AloCelyvir is an experimental cell-based therapy combining modified bone marrow cells with the ICOVIR-5 virus. This innovative approach aims to use the body’s own cells, modified to potentially attack cancer cells, to fight these aggressive brain tumors. The exact mechanism is still under investigation, but the therapy represents an advanced treatment strategy different from traditional chemotherapy or targeted medications.
Summary
Five clinical trials are currently ongoing for brain stem glioma, specifically focusing on DIPG and diffuse midline gliomas. These trials are distributed across seven European countries: Denmark, France, Italy, Netherlands, Poland, Spain, and Sweden.
A notable observation is the focus on combination therapies rather than single-drug approaches. Most trials combine novel medications with radiotherapy, reflecting the aggressive nature of these tumors and the need for multi-pronged treatment strategies. ONC201 appears in two trials, suggesting particular interest in this medication’s potential effectiveness.
The trials demonstrate diverse therapeutic approaches, from targeted small molecules (ONC201, everolimus, paxalisib, sirolimus, trametinib) to monoclonal antibodies (nimotuzumab) to innovative cell-based therapies (AloCelyvir). Several trials emphasize personalized medicine, using molecular profiling to guide treatment selection based on specific genetic markers in each patient’s tumor.
All trials focus exclusively on pediatric and young adult populations, with age ranges typically spanning from early childhood through early adulthood, reflecting the demographics most affected by these aggressive brain tumors. The studies measure various outcomes including progression-free survival, overall survival, safety profiles, and quality of life, providing comprehensive data to guide future treatment development.
