A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours
ConditionLow-grade Glioma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age6-25
SponsorIpsen
About this trial
The purpose of this study is to evaluate safety and the way the body absorbs, distributes and gets rid of the study drug tovorafenib in the body in Japanese children, adolescents and young adults with specific brain tumours. This includes how the drug is absorbed, distributed and eliminated from the body (called pharmacokinetics). The study will also test how well the drug works to shrink brain tumours.
In this study, all participants will receive tovorafenib orally once weekly.
There will be four periods in this study:
1. Screening period (up to 4 weeks): Participants will be evaluated to determine if they can take part in the study, requiring at least one visit to the study centre. 2. Treatment period (up to 24 months): All eligible participants will receive tovorafenib.
This requires five visits for the first 2 months (Cycle 1 and Cycle 2) followed by one visit every month (at the start of each treatment cycle). Participants will receive the first oral dose of tovorafenib on Day 1 of Cycle 1 at the study clinic. After Day 1, participants will need to take tovorafenib once weekly on Day 8, Day 15 and Day 22. Participants will be required to come to the study clinic in person at least five times for Cycle 1 and Cycle 2.
In addition, participants will have one remote visit (telephone call) during Cycle 1. After Cycle 2, only one in-person clinic visit is required at the start of each treatment cycle. A participant will stop treatment if their disease gets worse, if treatment has a harmful effect, or if they do not want to take part in the study anymore. 3. End-of-Treatment Safety Follow-Up (30 days): Participants will have a clinic visit 30 days after stopping treatment to check their health. 4. Long-Term Follow-Up (up to 2 years): Participants will be monitored every 3 months unless they start a new anti-cancer treatment or leave the study.
During the study, participants will undergo various health measurements and observations, including blood sampling and urine collections. Each participant will be in this study for up to approximately 4 years. Tovorafenib will be provided to participants who tolerate it for as long as their disease does not progress.
Once tovorafenib becomes approved and commercially available in Japan, participants may transition to the commercial drug for continued treatment.
A participant may withdraw consent to participate at any time.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must be 6 months to 25 years of age, inclusive, with at least two generations of Japanese ancestry at the time of signing the informed assent/consent.
Participants must have relapsed or progressive low-grade glioma with a documented known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions, as identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments-certified or other similarly certified laboratories.
Participants must have histopathologic verification of malignancy at either original diagnosis or relapse.
Participants must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
Disqualifiers
Participant's tumour has an additional previously known or expected to be activating molecular alteration(s) (e.g. histone mutation, isocitrate dehydrogenase 1 and 2 mutations, fibroblast growth factor receptor mutations or fusions, MYBL v-myb avian myeloblastosis viral oncogene homolog-like alterations, neurofibromatosis type-1 somatic or germline mutations).
Participant has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease.
Participant has known or suspected diagnosis of neurofibromatosis type 1 via genetic testing or current diagnostic criteria.
Participant has history of any major disease (e.g. confirmed or suspected diagnosis of interstitial lung disease), other than the primary malignancy under study, that in the opinion of the investigator might interfere with safe protocol participation.
Trial design
Design model
Single group
Treatments tested in this trial
Tovorafenib
DrugTablet or powder for reconstitution / powder for oral suspension
Treatment groups
6 Participants
are divided into 1 treatment groupGroup A: TovorafenibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Percentage of participants experiencing Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
Time frame
From first dose until 30 days post-treatment2
Percentage of participants experiencing Serious Adverse Events (SAEs) and AESIs
An Adverse event (AE) is any untoward medical occurrence, temporally associated with the use of study intervention, whether or not related to the study intervention.
Time frame
Up to 4 years from first dose, including post-treatment monitoring3
Area under the plasma concentration-time curve from time zero to last measurable concentration (AUC₀-t) of tovorafenib following a single dose
AUC₀-t represents the total drug exposure over time from administration until the last measurable concentration after a single dose of tovorafenib.
Time frame
From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)4
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC₀-inf) of tovorafenib following a single dose
AUC₀-inf estimates the total drug exposure from administration to infinite time, extrapolating beyond the last measurable concentration.
Time frame
From Cycle 1 Day 1 to Cycle 2 Day 8 (each cycle is 28 days)Secondary outcomes
1
Change in total tumor volume over time
Assessment based on MRI imaging data to evaluate tumor volume and its evolution during treatment.
Time frame
Every 12 weeks from Cycle 1 Day 1 up to end of treatment (approximately 24 months). Source ClinicalTrials.gov