A follow-up study on treatment with dabrafenib and/or trametinib for pediatric brain tumors

CNS tumors are growths in the central nervous system—that is, in the brain or spinal cord. In children and adolescents, they are among the most common solid tumors and can follow a wide variety of courses. Depending on the type of tumor, they grow slowly (low-grade) or more rapidly and thus more aggressively (high-grade). Because a child’s brain is particularly sensitive, even benign tumors can cause symptoms.

Mutations (genetic changes) in the genetic material of tumor cells play an important role in pediatric CNS tumors, as they can provide clues about the tumor’s behavior and potential treatment options. One such mutation is the BRAF V600E mutation, in which cells continuously receive a growth signal via the so-called MAPK signaling pathway. This signaling pathway can be specifically targeted by drugs such as dabrafenib and trametinib.

As a standard practice, depending on the location, size, and symptoms, surgery is typically performed first to remove the tumor completely or partially. If surgery is insufficient or not possible, chemotherapy usually follows as the standard first-line treatment, for example, with carboplatin and vincristine.

For tumors with a confirmed BRAF V600E mutation, targeted drugs are now available that specifically interfere with the disrupted signaling pathway (BRAF inhibitors). These so-called targeted therapies have been studied in clinical trials and are now available as a new treatment option, including as first-line therapy in place of chemotherapy.

The active ingredients dabrafenib and trametinib enhance each other’s effects by blocking the BRAF V600E mutation as well as other sites in the MAPK signaling pathway. The combination of these drugs is already approved for children aged 1 year and older with certain low- or high-grade brain tumors (gliomas) when systemic therapy is required. This follow-up study also includes patients who received only one of the two drugs as part of their original treatment, e.g., for medical reasons. Since both drugs are relatively new and have mostly been used in clinical trials to date, it is important to collect long-term data to understand potential long-term effects.

The goal of this Phase 4 study is therefore to collect data from patients who have previously been treated with dabrafenib and/or trametinib as part of clinical trials. The current therapy will be continued as it was initiated during the previous trial treatment. In addition, regular medical checkups will be conducted to assess efficacy, tolerability, and potential long-term effects. The physical growth, development, and general well-being of the children and adolescents will also be monitored. Follow-up as part of the study will continue for approximately 7 years.

Children, adolescents, and adults (former pediatric study participants) are eligible to participate, provided they were treated with dabrafenib and/or trametinib in one of the aforementioned preliminary studies (CTMT212X2101, CDRB436G2201, or CDRB436A2102). A prerequisite is that the treating physicians consider continuing the therapy to be appropriate. New patients who would be starting the therapy for the first time are not eligible.