​​Vorasidenib for the treatment of IDH-mutant astrocytoma after standard chemoradiotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Jan 2026 → ongoing

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Servier Affaires Médicales

External identifiers

EU CT number

2024-519404-27-00

ClinicalTrials.gov

NCT06809322

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Others

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 objectives 8

1. To investigate the effect of vorasidenib versus placebo on centrally assessed PFS from enrolment.
2. To evaluate PFS from the start of radiotherapy in participants receiving vorasidenib compared to placebo.
3. To assess the impact of vorasidenib maintenance therapy on overall survival (OS) compared to placebo.
4. To determine the response of vorasidenib maintenance therapy versus placebo.
5. To measure the time to next intervention (TTNI) for participants on vorasidenib maintenance therapy compared to placebo.
6. To compare the frequency and severity of adverse events (AEs) between the vorasidenib and placebo.
7. 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.
8. To investigate changes in neurocognitive function and seizure activity in patients receiving vorasidenib maintenance therapy compared to placebo.

Conditions and MedDRA coding

​​IDH-mutant grade 2 or 3 astrocytoma​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Informed consent
2. 2. Age ≥ 18 years
3. 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. 4. At least 1 prior surgery for glioma.
5. 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. 6. Last chemotherapy dose of first line chemoradiotherapy more than 6 weeks and less than 12 weeks before enrolment.
7. 7. Recovered from any clinically relevant toxicity of the previous chemoradiotherapy unless stable and manageable per investigator´s judgement
8. 8. Adequate bone marrow, renal, and hepatic function, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at or below ULN.
9. 9. WHO performance status 0-2
10. 10. Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrolment.
11. 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. 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.

Exclusion criteria 5

1. 1. Presence of 1p19q co-deletion, per local assessment.
2. 2. Tumour recurrence or progression per RANO 2.0 criteria between first day of radiotherapy and enrolment, per local assessment
3. 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. 4. Integrated diagnosis of astrocytoma, IDH-mutated, CNS5 WHO grade 4
5. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is PFS, as assessed locally from the date of enrolment using the RANO 2.0 criteria.

Secondary endpoints 9

1. PFS by retrospective central radiological assessment from the date of enrolment using the RANO 2.0 criteria.
2. PFS from the start of radiotherapy (both local and retrospective central radiological assessment) using RANO 2.0 criteria.
3. OS from date of enrolment.
4. 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.
5. TTNI
6. Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
7. HRQoL will be assessed
8. Neurological symptoms and signs, assessed using the NANO scale and measured by neurological progression-free survival (NPFS) and Seizure Control Composite Score Index.
9. Neurocognitive function, as assessed by a test battery consisting of HVLT-R, TMT, COWA test, and MOS scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Sponsor organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Stéphanie Kromar

Public contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Vassilis Golfinopoulos

Third parties 7

Locations

8 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications