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
UCLA
Los Angeles, California, United States
RECRUITINGLurie Children' sNWU
Chicago, Illinois, United States
RECRUITINGDana Farber (DFCI)
Boston, Massachusetts, United States
RECRUITINGChildren's Minnesota
Minneapolis, Minnesota, United States
RECRUITINGKids Cancer Centre, Sydney Children's Hospital Randwick
Sydney, Australia
RECRUITINGAdverse 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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