Ongoing Clinical Trials for Atypical Teratoid/Rhabdoid Tumour of CNS
Currently, there are 2 ongoing clinical trials investigating treatments for atypical teratoid/rhabdoid tumour of the central nervous system. These studies are testing various chemotherapy combinations and anti-angiogenic therapies in children diagnosed with this rare and aggressive brain tumor, conducted across multiple European countries.
Clinical trial locations
- Austria
- Belgium
- Czechia
- Denmark
- Finland
- France
- Germany
- Hungary
- Italy
- Netherlands
- Norway
- Spain
- Sweden
Study on Atypical Teratoid/Rhabdoid Tumors in Children Using Dactinomycin, Carboplatin, and Cyclophosphamide
This trial is evaluating treatment approaches for children diagnosed with atypical teratoid/rhabdoid tumors. The study aims to determine whether different consolidation therapies are effective in preventing the cancer from returning after initial treatment.
Who can participate:
The trial is designed for children under 18 years of age at the time of diagnosis. Participants must have confirmed diagnosis through tissue examination showing loss or deficiency of specific proteins (INI1, SMARCB1, or SMARCA4). The trial has three different parts (A, B, and C), each with slightly different age requirements:
- Part A enrolls children aged 12 to 35 months who respond well to initial chemotherapy
- Part B is for children under 12 months or those who cannot receive radiotherapy
- Part C includes children aged 36 months or older, or those who cannot receive high-dose chemotherapy
All participants must have adequate organ function, including normal liver function (with ALT or AST less than 3 times the upper normal limit), kidney function (creatinine less than 1.5 times normal and age-appropriate GFR), and heart function (ejection fraction of 50% or more). After three courses of initial chemotherapy, MRI and cerebrospinal fluid examinations must show that the disease is stable or improving. Written informed consent from parents or guardians is required according to national laws.
Who cannot participate:
Children who do not have confirmed atypical teratoid/rhabdoid tumors cannot join this study. Those outside the specified age ranges for each part of the trial are also excluded. Children who are not suitable for the specific treatment plans outlined in the study, such as high-dose chemotherapy or radiation therapy, cannot participate. Those who are not eligible for randomization within Part A of the study are also excluded.
Trial focus and goals:
The main goal is to evaluate whether high-dose chemotherapy and focal radiotherapy work as well as or better than current standard treatments. The study compares outcomes of children receiving these new approaches to those receiving standard care and historical patient data. For children aged 12 to 35 months, researchers are specifically comparing three courses of high-dose chemotherapy to radiotherapy. The trial follows participants over several years to assess overall survival and other health outcomes, including neurocognitive function and quality of life.
Investigational drugs:
The study uses a combination of chemotherapy medications including dactinomycin, carboplatin, cyclophosphamide, ifosfamide, etoposide, vincristine sulfate, thiotepa, doxorubicin hydrochloride, and methotrexate. These are administered intravenously (directly into a vein) during the induction phase. The consolidation phase involves either high-dose chemotherapy or focal radiotherapy, depending on the child’s age and response to initial treatment. High-dose chemotherapy uses very high doses of powerful drugs to eliminate remaining cancer cells, while focal radiotherapy uses high-energy rays to target and destroy cancer cells in specific areas. Some children will also receive conventional chemotherapy alongside other treatments.
Study on the Effectiveness of Bevacizumab and Drug Combination for Children with Recurrent or Progressive Medulloblastoma, Ependymoma, and ATRT
This trial explores treatment options for children whose brain tumors have returned or continued to grow despite previous treatment. The study focuses on using medications that target the blood vessels feeding the tumor, combined with lower, more frequent doses of chemotherapy.
Who can participate:
Children and young people from birth up to 20 years of age at the time of original diagnosis are eligible if they have recurrent or progressive medulloblastoma, ependymoma, or atypical teratoid rhabdoid tumor. The disease must have returned or worsened, with at least one site that has not been previously re-treated. The original diagnosis or relapse must be confirmed through tissue examination under a microscope.
Participants must have adequate organ and bone marrow function. This includes liver function with ALT less than 5 times the normal limit, kidney function with creatinine less than 1.5 times the age-appropriate normal limit, white blood cell count greater than 1000 per mm3, and platelet count greater than 20,000 per mm3. If blood counts are lower (white blood cells less than 2000 or platelets less than 50,000), treatment will begin at a reduced dose.
Participants must have a performance status score of at least 50, meaning they can perform most daily activities with some assistance. For children under 12, this is measured using the Lansky play scale. Written informed consent must be provided by parents or guardians after understanding the study details.
Who cannot participate:
Children whose tumors do not match the specified types (medulloblastoma, ependymoma, or atypical teratoid rhabdoid tumor) or who fall outside the age range cannot participate. Those considered part of vulnerable populations who might need special protection are also excluded.
Trial focus and goals:
The study aims to determine how well a combination of medications works in stopping tumor growth. This approach combines two strategies: metronomic therapy, which uses lower doses of chemotherapy given more frequently to minimize side effects while continuously attacking cancer cells, and anti-angiogenic therapy, which stops the formation of new blood vessels that tumors need to grow. By cutting off the blood supply, this treatment aims to starve the tumor and prevent it from getting nutrients needed to expand.
Researchers will evaluate tumor response at 6 months, looking for complete response, partial response, stable disease, or lack of recurrence. Follow-up assessments occur at 6, 12, 24, and 36 months to evaluate overall survival, progression-free survival, quality of life, and performance status. The study also monitors safety and manages any side effects that arise during treatment.
Investigational drugs:
The trial uses a combination of seven medications: cytarabine (given as an injection into the space around the spinal cord), celecoxib (oral capsule), cyclophosphamide (oral solution), etoposide (intravenous infusion), bevacizumab (intravenous infusion), fenofibrate (oral capsule), and thalidomide (oral capsule). These medications work together to target cancer cells and prevent the growth of blood vessels that feed the tumor. The metronomic approach involves giving these drugs at lower doses more frequently, while the anti-angiogenic components specifically target the tumor’s blood supply.
Summary
Both ongoing trials for atypical teratoid/rhabdoid tumour of the central nervous system are focused exclusively on pediatric populations, reflecting the fact that this aggressive brain tumor predominantly affects young children. The trials are widely distributed across Europe, with particularly strong representation in Scandinavia (Sweden, Norway, Denmark, Finland) and Central Europe (Germany, France, Czechia, Spain).
The first trial takes a comprehensive approach by evaluating newly diagnosed patients and comparing different consolidation therapies based on age groups. It employs intensive multi-drug chemotherapy regimens followed by either high-dose chemotherapy or radiotherapy. The second trial specifically addresses the challenging situation of recurrent or progressive disease, testing a novel combination of metronomic chemotherapy with anti-angiogenic therapy that aims to cut off the tumor’s blood supply.
Both studies emphasize long-term monitoring of participants, tracking not only survival but also quality of life and neurocognitive outcomes, which is particularly important for young patients whose brains are still developing. The trials require careful screening to ensure participants have adequate organ function before beginning these intensive treatments, and both provide options for dose adjustments based on individual tolerance.
