The objective of this study is to evaluate the safety, tolerability, efficacy profile, and effect on growth and development of vorasidenib in pediatric participants aged 12 to \< 18 years old with grade 2 glioma with an IDH1 or IDH2 mutation. The study includes a screening period, a treatment period consisting of continuous 28-day cycles of treatment, a safety follow-up period and a long-term follow-up period. The long-term follow-up period will assess participants for growth, development, and long-term safety impacts for approximately 5 years after the start of treatment or until Tanner Stage V is reached (whichever is later). Participants may undergo blood tests, heart tests (electrocardiogram (ECG)), imaging (MRI, X-ray), vital sign checks, and physical exams.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
40mg taken orally daily for participants weighing ≥ 40 kg OR 20mg taken orally daily for participants weighing ≥ 25 kg to \< 40 kg
Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events (AEs) leading to discontinuation, or Adverse Events (AEs) leading to death
Time frame: From start of treatment through 28 days after last dose for AEs (Safety follow-up), study-related SAEs will be reported through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Severity of AEs
As assessed by the NCI-CTCAE version 5.0.
Time frame: From start of treatment through 28 days after last dose for AEs (Safety follow-up), study-related SAEs will be reported through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Height and Weight Percentiles at Study Visits
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change in Height and Weight Percentiles from Cycle 1 Day 1 (C1D1)
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Tanner staging
Tanner stages represent puberty progression from stage 1 being the prepubertal form to stage 5 representing the final adult form.
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Average age of menarche
Historically and/or while on treatment, if applicable
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of leutenizing hormone (LH)
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of follicle-stimulating hormone (FSH)
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of anti-Müllerian hormone (AMH)
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of estradiol
For females only
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of testosterone
For males only
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Change from C1D1 to the worst on-treatment value of Insulin-like growth factor 1 (IGF-1)
Time frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days long)
Change from C1D1 to the worst on-treatment value of Insulin-Like Growth Factor-Binding Protein 3 (IGFBP-3)
Time frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days long)
Change from C1D1 to the worst on-treatment value of thyroid stimulating hormone (TSH)
Time frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days long)
Change from C1D1 to the worst on-treatment value of Free T4 (thyroxine)
Time frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days long)
Change from C1D1 to the worst on-treatment hand/wrist bone age as determined by X-ray
Time frame: From start of treatment through long-term follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Progression-free survival (PFS)
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Objective response (OR)
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Best overall response of complete response (CR), partial response (PR), or minor response (mR)
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Time to response (TTR)
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Time to CR, PR, or mR
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Duration of response (DoR)
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Duration of CR, PR, or mR
Time frame: Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years)
Plasma concentration of vorasidenib
Time frame: Through Cycle 3 Day 1 (C3D1) (each cycle is 28 days long)
Plasma concentration of AGI-69460
Time frame: Through Cycle 3 Day 1 (C3D1) (each cycle is 28 days long)
Institut de Recherches Internationales Servier (I.R.I.S.)
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