Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients With Refractory Histiocytosis or After the Failure of Vemurafenib Treatment

What this Trial Is About

Researchers are evaluating the optimal timing and dosage of trametinib for juvenile patients with histiocytosis who do not have the BRAF gene mutation or who have not responded to vemurafenib treatment. This trial is part of the larger POLHISTIO project, which aims to improve diagnosis and treatment for children with histiocytosis by studying gene mutations and their impact on treatment outcomes. The study focuses on patients resistant to conventional therapies and seeks to personalize treatment based on molecular testing and disease activity. Participants receive trametinib, with dosing adjusted by age: less than 6 years old receive 0.032 mg/kg and those 6 years or older receive 0.025 mg/kg. The study randomly assigns patients to different durations of trametinib treatment, with one group tested for mutations or disease activity over three consecutive three-month intervals and another group over five such intervals. The trial is open-label and non-commercial, conducted at a single center. During the study, participants undergo molecular testing of circulating tumor DNA and clinical assessments at regular intervals to monitor disease progression and response to treatment. Researchers measure event-free survival over two years as the primary outcome, along with molecular relapse and time to negative mutation results. Participants are closely monitored for safety, and the study continues with follow-up assessments to evaluate long-term treatment effects and disease control.

Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients