Vorasidenib Study in Pediatric Participants With Grade 2 Astrocytoma or Oligodendroglioma With an IDH1 or IDH2 Mutation

Servier

Status and phase

Begins enrollment in 1 month

Phase 2

Conditions

Grade 2 Astrocytoma or Oligodendroglioma With an IDH1 or IDH2 Mutation

Treatments

Drug: Vorasidenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT07286292

S095032-236

Details and patient eligibility

About

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.

Enrollment

10 estimated patients

Sex

All

Ages

12 to 17 years old

Volunteers

No Healthy Volunteers

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.
Have:
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 ≥ 70. 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.
Have adequate bone marrow function as evidenced by:
Absolute neutrophil count ≥ 1500/mm3 or ≥ 1.5 × 109/L
Hemoglobin ≥ 9 g/dL
Platelets ≥ 100,000/mm3 or ≥ 100 × 109/L
Have adequate hepatic function as evidenced by:
Serum total bilirubin ≤ 1.5 × ULN; if > 1.5 ULN and due to Gilbert syndrome, total bilirubin ≤ 3 × ULN with direct bilirubin ≤ ULN
AST at or below ULN and ALT at or below ULN
Alkaline phosphatase (ALP) ≤ 2.5 × ULN
Have adequate renal function as evidenced by:
Serum creatinine ≤ 2.5 × ULN, OR
eGFR > 40 mL/min/1.73 m2 based on the Bedside Schwartz method 0.413 × (Height in cm/Serum Creatinine in mg/dL)
Have recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management (functional limitations as a result of prior surgical resections or due to the anatomical location of the tumor will be permitted).
Female participants of reproductive potential must have a negative serum pregnancy test before starting investigational medicinal product (IMP).
Women of childbearing potential as well as fertile male participants with female partners of reproductive potential, must agree to abstain from sexual intercourse or to use 2 effective methods of contraception from screening until at least 90 days after the last dose of IMP.

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 C1D1.
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.
Have a heart-rate corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events.
Are taking therapeutic doses of steroids (defined as > 1.5 mg/day dexamethasone or >10 mg/day prednisone or equivalent) for signs/symptoms of glioma. Participants taking physiologic doses (defined as ≤ 1.5 mg/day dexamethasone or ≤ 10 mg/day prednisone or equivalent) for medical conditions not related to glioma will be permitted.
Are taking any medications that are CYP2C19 or CYP3A substrates with a narrow therapeutic index or strong inhibitors of CYP1A2.
Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus (HIV) antibody results, or AIDS-related illness. Participants with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Participants with chronic HBV or HIV that is adequately suppressed by institutional practice will be permitted.
Have known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally. Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
Have any other acute or chronic medical or psychiatric condition.