This study combines two pediatric glioma cohorts (LGG and HGG cohorts) into a
multi-center, open-label, Phase II study:
- The LGG cohort is a multi-center, randomized, open-label part of this Phase II study
conducted in children and adolescent patients with BRAF V600 mutation-positive LGG
whose tumor was unresectable and who required first systemic treatment. Participants
in the LGG cohort were randomized in a 2:1 ratio to either dabrafenib plus
trametinib or carboplatin with vincristine.
- The HGG cohort is a multi-center, single-arm, open-label part of this Phase II study
conducted in children and adolescent patients with BRAF V600 mutation-positive,
refractory or relapsed HGG tumors after having received at least one previous
standard therapy.
The duration of treatment for participants on dabrafenib plus trametinib in LGG and for
all patients in the HGG cohort was continued until the loss of clinical benefit in the
opinion of the Investigator, unacceptable toxicity, start of a new anti-neoplastic
therapy, discontinuation at the discretion of the investigator or patient/legal guardian,
lost to follow-up, death, study termination by the sponsor, or until disease progression.
The duration of treatment for patients in the carboplatin with vincristine arm in LGG
cohort was continued for the prescribed number of cycles, as tolerated or until
unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the
discretion of the investigator or patient/legal guardian, lost to follow-up, death, study
is terminated by the sponsor or until disease progression. Participants randomized to the
carboplatin with vincristine treatment arm were allowed to cross over to receive
dabrafenib in combination with trametinib after centrally confirmed RANO-defined disease
progression. Crossover was allowed during the treatment period or the post-treatment
period.
After discontinuation of study treatment, all participants (LGG and HGG cohorts) were
followed for safety for at least 30 days after the last dose of study treatment. All
participants who discontinued study treatment for reasons other than disease progression,
death, loss to follow up, or withdrawal of consent moved into the post-treatment efficacy
follow-up phase. Finally, all participants were followed for survival once they
discontinued study treatment for at least 2 years after the last patient first study
treatment (except if consent was withdrawn, death, or the patient was lost to follow-up
or discontinued study)
