Who can enter
- Children, adolescents and young adults with pLGG with a RAF alteration requiring treatment for the first time
- Age: younger than 25
Goal
The goal of this study is to find out if DAY101 (also known as tovorafenib) is safe, well-tolerated and how well it works compared to Standard of Care (SoC) chemotherapy in treating children, adolescent, and young adult patients with pLGG with a RAF alteration.
Background
Pediatric low-grade gliomas are the most common brain tumor diagnosed in children. They can occur anywhere in the central nervous system and are serious, life-altering, and potentially fatal with significant disease- and treatment-associated morbidity. Low-grade glioma patients often suffer from significant damage to important functional structures of the brain particularly when located in central midline structures. The disease does not only compromise overall survival, but rather causes long-term functional damage to key functions of the brain.
Standard of Care chemotherapy is currently used to treat children, adolescents and young adults with pLGG with a RAF mutation for the first time. Sometimes, these chemotherapies don’t work well or cause treatment-related morbidities and long-term cognitive impairments. Therefore, there is a need to develop additional effective treatment options.
DAY 101 is an oral pan-RAF inhibitor. It works by directly inhibiting the mutations that are causing tumor growth. Patients with pLGG who have these mutations may benefit from treatment with an inhibitor such as DAY101. It could prevent, or at least delay, the need for more toxic alternative therapies such as systemic chemotherapy or radiation.
There have been studies already completed with this drug in adults and children and there are ongoing studies in adult and children with pLGG. Thus far, DAY101 has been generally well-tolerated in pediatric patients.
Most currently applied chemotherapy regimens require in-clinic intravenous treatment. Patients randomized to DAY101 in this study will receive an oral drug. The drug can be taken at home, allowing continuation of daily activities such as attending school.
Information from this study will help doctors learn more about the study drug as a treatment for pLGG. This information may help future cancer patients.
Patients who join this study will be assigned by chance (like the flip of a coin) to receive either DAY101 or SoC chemotherapy (50-50 chance). SoC chemotherapy will include several options of vincristine/carboplatin or vinblastine that are used in standard medical practice in the treatment of pLGG. The investigator will determine which SoC chemotherapy the patient will be given if a patient is assigned to SoC chemotherapy.
Treatment will be given in cycles. For DAY101, the cycles have a duration of 4 weeks (28 days). For SoC chemotherapy, the cycles are specific to the SoC chemotherapy regimen the patient will receive and are 4 to 6 weeks long. Treatment in the study may be continued as long as the tumor does not grow or the patient does not have side effects which cannot be tolerated.