Ongoing Clinical Trials for Malignant Central Nervous System Neoplasm
There are currently 3 ongoing clinical trials for patients with malignant central nervous system neoplasm, testing innovative therapies including CAR T-cell therapy and targeted inhibitors. These trials are being conducted across multiple European countries, offering treatment options for children and young adults with relapsed or refractory brain tumors.
Clinical trial locations
- Czechia
- Denmark
- France
- Germany
- Ireland
- Italy
- Study on the Safety of Anti-GD2 CAR T Cells, Cyclophosphamide, and Fludarabine in Children and Young Adults with Relapsed or Refractory Brain Tumors
- Study on Larotrectinib for Treating Children with Advanced Solid Tumors with NTRK Fusion
- Study on the Effects of Selpercatinib in Children with Advanced RET-Altered Solid Tumors or Primary Central Nervous System Tumors
- Netherlands
- Spain
- Sweden
Study on the Safety of Anti-GD2 CAR T Cells, Cyclophosphamide, and Fludarabine in Children and Young Adults with Relapsed or Refractory Brain Tumors
This trial focuses on testing a novel immunotherapy approach for young patients whose brain tumors have returned or are not responding to standard treatments. The study uses specially modified immune cells called anti-GD2 CAR T cells, which are designed to recognize and attack cancer cells more effectively.
Main inclusion criteria: Patients must be between 6 months and 30 years old with a confirmed diagnosis of relapsed or difficult-to-treat central nervous system tumor, including medulloblastoma or high-grade glioma. The tumor must show GD2 positivity, a specific marker that makes patients eligible for this treatment. Participants need to have a Karnofsky or Lansky score of at least 60, indicating they can perform daily activities reasonably well. Recent imaging tests must be completed within 14 days before treatment begins, and patients must have recovered from severe side effects of previous treatments. An implantable device for delivering medication directly into the brain is required, and patients must have suitable vein access for a procedure called apheresis.
Main exclusion criteria: Patients with tumor types other than relapsed or refractory malignant central nervous system tumors cannot participate. Those outside the specified age range, pregnant or breastfeeding women, and patients with serious health conditions that could interfere with the study are excluded. Individuals currently participating in another clinical trial or with allergies to study treatment components are also ineligible.
Trial focus: The study aims to evaluate the safety and determine the best dose of anti-GD2 CAR T cells. The treatment involves preparing the body with chemotherapy drugs Cyclophosphamide and Fludarabine before infusing the modified T cells. Researchers will monitor how the body responds to treatment and how long the modified cells remain active. Regular MRI scans will track tumor size and growth throughout the study, which is expected to continue until 2038.
Investigational drug: The main treatment is iC9-GD2-CAR T cells, which are the patient’s own immune cells modified in the laboratory to express a receptor targeting the GD2 antigen commonly found on certain tumor cells. This cell-based immunotherapy is administered through infusion and represents a cutting-edge approach to treating resistant brain tumors.
Study on Larotrectinib for Treating Children with Advanced Solid Tumors with NTRK Fusion
This multi-country European trial investigates larotrectinib, an oral medication for children with tumors that have a specific genetic change called NTRK fusion. The study is divided into two phases: the first focuses on safety, and the second evaluates how well tumors respond to treatment.
Main inclusion criteria: Patients must have solid tumors with confirmed NTRK fusion. For Phase 1, which is now closed, participants ranged from birth to 21 years with tumors that had returned, worsened, or not responded to other treatments. Phase 2 includes infants with locally advanced or metastatic infantile fibrosarcoma, as well as patients from birth to 21 years with solid or central nervous system tumors that have NTRK gene fusion. Patients with NTRK-fusion positive benign tumors are also eligible. Participants must have a performance score of at least 50 on the Karnofsky or Lansky scale and demonstrate adequate blood cell counts, liver function, and kidney function.
Main exclusion criteria: Patients without solid tumors showing NTRK fusion cannot participate. Those outside the specified age range or unable to take medication orally are excluded. Pregnant or breastfeeding women, patients with other medical conditions that might interfere with the study, and those currently participating in another clinical trial are ineligible. Patients who have had certain recent treatments may need to wait before joining the study.
Trial focus: The primary goal is to determine the safety of larotrectinib and identify any side effects while assessing its effectiveness in shrinking or controlling tumors. An independent radiology review committee evaluates tumor responses, looking for complete or partial reduction in tumor size. The study monitors participants closely throughout treatment to gather information about benefits and risks.
Investigational drug: Larotrectinib is an oral medication available as a hard capsule or oral solution. It works by inhibiting TRK proteins, which are involved in the growth of cancer cells with NTRK fusions. This targeted therapy has been approved for treating solid tumors with these specific genetic alterations.
Study on the Effects of Selpercatinib in Children with Advanced RET-Altered Solid Tumors or Primary Central Nervous System Tumors
This trial examines selpercatinib, an oral medication targeting tumors with changes in the RET gene. The study includes children and young adults with advanced solid tumors or brain and spinal cord tumors that have specific RET alterations.
Main inclusion criteria: Patients must be between 12 and 21 years old with solid or primary central nervous system tumors that have returned, worsened, or not responded to available treatments. Participants need adequate blood health, including sufficient white blood cells, platelets, and hemoglobin without recent medical support. Liver, pancreas, and kidney function must meet specific health standards. Evidence of a RET gene change in the tumor or blood, identified through testing, is required. Patients must have a Karnofsky or Lansky performance score of at least 50 and be able to swallow capsules or take medicine through a tube if needed. Those with brain tumors or brain metastasis must have stable neurological symptoms and not require increasing doses of steroids before joining the study.
Main exclusion criteria: Patients without advanced RET-altered solid tumors or primary central nervous system tumors cannot participate. Those outside the specified age range, unable to take selpercatinib due to allergies or other medical reasons, or with conditions that might interfere with the study are excluded. Pregnant or breastfeeding women, patients currently in another clinical trial, those who haven’t recovered from previous treatments, and individuals with certain heart conditions are ineligible.
Trial focus: The study is divided into two phases. Phase one determines the safety of selpercatinib and identifies potential side effects. Phase two evaluates how well tumors respond to treatment, measuring tumor size to see if they shrink or disappear. An independent review committee conducts objective assessments of treatment response. The study includes regular monitoring through physical exams, blood tests, and imaging studies, with the trial expected to continue until late 2024.
Investigational drug: Selpercatinib is an oral medication available in tablet or oral solution form. It is a RET inhibitor that targets and blocks the RET protein, which can contribute to tumor growth when altered. This investigational drug works at the molecular level by blocking RET protein activity, potentially slowing down or stopping cancer cell growth.
Summary
The three ongoing clinical trials for malignant central nervous system neoplasm demonstrate a strong focus on precision medicine approaches for pediatric and young adult patients. All three studies target specific genetic alterations in tumors: GD2 positivity, NTRK fusion, and RET alterations. This reflects the growing understanding that brain tumors with particular molecular characteristics may respond to targeted therapies.
Geographically, these trials show significant concentration in Western European countries, with Italy participating in all three studies. Germany, France, Denmark, and Spain each host two trials, while Czechia, Ireland, Netherlands, and Sweden participate in one study each. This distribution suggests robust clinical research infrastructure across Europe for pediatric oncology.
The trials employ different therapeutic approaches: the Italian study uses innovative CAR T-cell immunotherapy requiring specialized facilities and long-term follow-up until 2038, while the two multi-country studies test oral targeted inhibitors with more manageable administration. All three studies focus exclusively on relapsed or refractory cases, addressing an urgent need for treatment options when standard therapies have failed.
Patient selection criteria across all trials emphasize adequate organ function and performance status, reflecting the need to balance treatment potential with patient safety. The inclusion of very young patients, starting from birth in some trials, highlights the particular challenges of pediatric brain tumors and the need for age-appropriate therapeutic options.
