A Phase 2, Single Arm, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Vorasidenib in Pediatric Participants Aged 12 to < 18 Years Old With Grade 2 Astrocytoma or Oligodendroglioma With an IDH1 or IDH2 Mutation
Overview
- Phase
- Phase 2
- Intervention
- Vorasidenib
- Conditions
- Not specified
- Sponsor
- Institut de Recherches Internationales Servier (I.R.I.S.)
- Enrollment
- 10
- Primary Endpoint
- Height and Weight Percentiles at Study Visits
- Status
- Not Yet Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Weigh ≥ 25 kg at Screening.
- •Written informed consent/assent must be obtained from a legally authorized representative, and assent must be obtained from the participant in accordance with local regulations. Participants and their families must be willing and able to comply with the scheduled visits, treatment plans, procedures, and laboratory tests, including serial peripheral blood sampling, during the study.
- •Have Grade 2 astrocytoma or oligodendroglioma per World Health Organisation (WHO) 2021 criteria.
- •Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection) and no other prior anticancer therapy, including chemotherapy and radiotherapy, and do not need immediate chemotherapy or radiotherapy in the opinion of the Investigator.
- •Confirmed IDH1 or IDH2 gene mutation, as well as known 1p19q and/or ATRX (Alpha Thalassemia/Mental Retardation Syndrome X-linked) status based on local testing of tumor tissue by an accredited laboratory.
- •For astrocytoma: Absence of 1p19q co-deletion and/or documented loss of nuclear ATRX expression or ATRX mutation by local testing.
- •For oligodendroglioma: Presence of 1p19q co-deletion by local testing.
- •Have magnetic resonance imaging (MRI)-evaluable, measurable, non-enhancing disease
- •Have a Karnofsky Performance Score (KPS; for participants ≥ 16 years of age) or Lansky Play-Performance Scale (LPPS; for participants \< 16 years of age) score of ≥
- •Karnofsky Performance Score and LPPS \< 70 due to functional limitations as a result of prior surgical resections or due to the anatomical location of the tumor will be permitted.
Exclusion Criteria
- •Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including, but not limited to, systemic chemotherapy, radiotherapy, vaccines, small molecule inhibitors, IDH inhibitors, and investigational agents.
- •Have features assessed as high-risk by the Investigator.
- •Have leptomeningeal disease.
- •Concurrent active malignancy except for curatively resected nonmelanoma skin cancer or curatively treated carcinoma in situ. Participants with previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening.
- •Unable to swallow oral medication.
- •Are pregnant or breastfeeding.
- •Are participating in another interventional study at the same time; participation in non-interventional registries or epidemiological studies is allowed.
- •Have a severe or uncontrolled active acute or chronic infection or an unexplained fever \> 38.5°C within 7 days of C1D
- •Have a known hypersensitivity to any of the components of vorasidenib.
- •Have significant active cardiac disease within 6 months before the start of IMP, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
Arms & Interventions
Open Label Vorasidenib
Intervention: Vorasidenib
Outcomes
Primary Outcomes
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)
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
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)
As assessed by the NCI-CTCAE version 5.0.
Tanner staging
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 stages represent puberty progression from stage 1 being the prepubertal form to stage 5 representing the final adult form.
Average age of menarche
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)
Historically and/or while on treatment, if applicable
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
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)
For females only
Change from C1D1 to the worst on-treatment value of testosterone
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)
For males only
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)
Secondary Outcomes
- Progression-free survival (PFS)(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Objective response (OR)(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)(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Time to response (TTR)(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Time to CR, PR, or mR(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Duration of response (DoR)(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Duration of CR, PR, or mR(Through PFS follow-up (approximately 5 years per participant for a total study duration of approximately 7 years))
- Plasma concentration of vorasidenib(Through Cycle 3 Day 1 (C3D1) (each cycle is 28 days long))
- Plasma concentration of AGI-69460(Through Cycle 3 Day 1 (C3D1) (each cycle is 28 days long))