Vorasidenib for the treatment of IDH-mutated astrocytoma after standard radiochemotherapy

Australia, Austria, Belgium, Canada, Czechia, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom (ICTRP)

Identifiant de l'essai ICTRP
CTIS2024-519404-27-00 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
Vorasidenib as maintenance treatment after first-line chemoradiotherapy in IDH-mutant grade 2 or 3 astrocytoma: a placebo-controlled, triple-blind, randomized phase III study (VIGOR) (BASEC)

Titre académique
EORTC-2427-BTG: Vorasidenib as maintenance treatment after first-line chemoradiotherapy in IDH-mutant grade 2 or 3 astrocytoma: a placebo-controlled, triple-blind, randomized phase III study (VIGOR) - EORTC-2427-BTG (ICTRP)

Titre public
??Vorasidenib for the treatment of IDH-mutant astrocytoma after standard chemoradiotherapy (ICTRP)

Maladie en cours d'investigation
??IDH-mutant grade 2 or 3 astrocytoma?
MedDRA version: 21.0Level: PTClassification code: 10060971Term: Astrocytoma malignant Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04] (ICTRP)

Intervention étudiée
Product Name: Placebo tablets to match S95032 drug product are supplied as film-coated tablets for oral administration., Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A , Product Name: S95032/AG-881, Product Code:PRD11331943, Pharmaceutical Form: FILM-COATED TABLET, Other descriptive name: , Strength: , Product Name: S95032/AG-881, Product Code:PRD11331944, Pharmaceutical Form: FILM-COATED TABLET, Other descriptive name: , Strength: (ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Number of treatment arms in the trial: (ICTRP)

Critères d'inclusion/exclusion
Inclusion criteria: 1. Informed consent, 10. Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrolment., 11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within two weeks prior to enrolment a serum or urine pregnancy test must be conducted and confirmed negative within 72 hours prior to the first dose of study treatment., 12. Participants of childbearing / reproductive potential should use two adequate methods of birth control, including a highly effective method and a barrier method during the study treatment period and for at least 90 days after the last dose of treatment., 2. Age = 18 years, 3. Integrated diagnosis of astrocytoma, IDH-mutant, CNS5 WHO grade 2 or 3, per local assessment, with documented IDH1 or IDH2 mutation based on local testing of tumour tissue., 4. At least 1 prior surgery for glioma., 5. Completed first-line standard of care radiotherapy (minimum 50.4 Gy, photons or protons allowed) followed by SoC adjuvant chemotherapy (i.e., either 4-12 cycles of temozolomide or 2-6 cycles of PCV)., 6. Last chemotherapy dose of first line chemoradiotherapy more than 6 weeks and less than 12 weeks before enrolment., 7. Recovered from any clinically relevant toxicity of the previous chemoradiotherapy unless stable and manageable per investigators judgement, 8. Adequate bone marrow, renal, and hepatic function, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at or below ULN., 9. WHO performance status 0-2 (ICTRP)

Exclusion criteria: 1. Presence of 1p19q co-deletion, per local assessment., 2. Tumour recurrence or progression per RANO 2.0 criteria between first day of radiotherapy and enrolment, per local assessment, 3. Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen., 4. Integrated diagnosis of astrocytoma, IDH-mutated, CNS5 WHO grade 4, 5. Ongoing use of medications that are CYP2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index. Participants must be transferred to other medications before receiving the first dose of study drug

Critères d'évaluation principaux et secondaires
Main Objective: In this phase III study, the main goal is to demonstrate that vorasidenib maintenance therapy improves locally assessed PFS from enrolment compared to placebo in patients with IDH-mutant, CNS5 WHO grade 2 or 3 astrocytoma following the completion of first-line chemoradiotherapy;Secondary Objective: To investigate the effect of vorasidenib versus placebo on centrally assessed PFS from enrolment., To evaluate PFS from the start of radiotherapy in participants receiving vorasidenib compared to placebo., To assess the impact of vorasidenib maintenance therapy on overall survival (OS) compared to placebo., To determine the response of vorasidenib maintenance therapy versus placebo., To measure the time to next intervention (TTNI) for participants on vorasidenib maintenance therapy compared to placebo., To compare the frequency and severity of adverse events (AEs) between the vorasidenib and placebo., To assess changes in health-related quality of life (HRQoL) in each treatment arm. To evaluate the impact of vorasidenib maintenance therapy on neurological symptoms and signs compared to placebo., To investigate changes in neurocognitive function and seizure activity in patients receiving vorasidenib maintenance therapy compared to placebo.;Primary end point(s): The primary endpoint is PFS, as assessed locally from the date of enrolment using the RANO 2.0 criteria. (ICTRP)

Secondary end point(s):PFS by retrospective central radiological assessment from the date of enrolment using the RANO 2.0 criteria.;Secondary end point(s):PFS from the start of radiotherapy (both local and retrospective central radiological assessment) using RANO 2.0 criteria.;Secondary end point(s):OS from date of enrolment.;Secondary end point(s):Best response, overall response, disease control and complete response rate (both local and retrospective central radiological assessment) as well as duration of response using RANO 2.0 criteria.;Secondary end point(s):TTNI;Secondary end point(s):Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.;Secondary end point(s):HRQoL will be assessed;Secondary end point(s):Neurological symptoms and signs, assessed using the NANO scale and measured by neurological progression-free survival (NPFS) and Seizure Control Composite Score Index.;Secondary end point(s):Neurocognitive function, as assessed by a test battery consisting of HVLT-R, TMT, COWA test, and MOS scale (ICTRP)

Date d'enregistrement
10.07.2025 (ICTRP)

Inclusion du premier participant
19.01.2026 (ICTRP)

Sponsors secondaires
non disponible

Contacts supplémentaires
Vassilis Golfinopoulos, vassilis.golfinopoulos@eortc.org, +3227741665, Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi (ICTRP)

ID secondaires
NCT06809322 (ICTRP)

Résultats-Données individuelles des participants
Yes (ICTRP)

Informations complémentaires sur l'essai
https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-519404-27-00 (ICTRP)