IDH-mutant Grade 2 or 3 AstrocytomaPhase 3VIGORNCT06809322
Vorasidenib Maintenance for IDH Mutant Astrocytoma
A Phase 3 study testing Vorasidenib in people with IDH-mutant Grade 2 or 3 Astrocytoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 59 sites in 12 countries.
Trial summary
The main goal of VIGOR is to demonstrate that vorasidenib maintenance therapy improves locally assessed progression-free survival (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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- IDH-mutant Grade 2 or 3 Astrocytoma
- What is being tested?
- Vorasidenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 468 participants
- Where
- 59 sitesin 12 countries
- Study dates
- 16 Jan 2026to 31 May 2037
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Before participant's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.
- Age ≥ 18 years
- Integrated diagnosis of astrocytoma, IDH-mutant, WHO CNS5 grade 2 or 3, per local assessment
- Documented IDH1 or IDH2 mutation based on local testing of tumour tissue
- At least 1 prior surgery for glioma (biopsy, partial resection, gross-total resection)
- 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).
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- Adequate bone marrow function: absolute neutrophil counts ≥ 1.5 x 109/L, haemoglobin ≥ 9 g/dL, platelets 100 x 109/ L.
- Adequate renal function: serum creatinine ≤ 2.0 x ULN, or creatine clearance > 40 mL/min, as calculated based on CKD-EPI 2021 formula.
- Adequate hepatic function:
- Total bilirubin ≤ 1.5 × ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin ≥1.5 × ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x ULN.
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN.
- Recovered from any clinically relevant toxicity of the previous chemoradiotherapy cycle unless stable and manageable per investigator´s judgement
- WHO performance status 0-2
- Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrollment.
- Baseline brain MRI available, as defined in the schedule of assessments
- Available FFPE tumour tissue from prior neurosurgery for central biobanking and translational research
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within two weeks prior to enrolment.
- 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.
Who cannot join
- Presence of 1p19q co-deletion, per local assessment.
- Tumour recurrence or progression per RANO 2.0 criteria between first day of radiotherapy and enrolment, per local assessment
- Last chemotherapy dose of first line chemoradiotherapy less than 6 weeks or more than 12 weeks before enrolment
- Prior therapy with an IDH inhibitor or IDH vaccine
- 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.
- Integrated diagnosis of astrocytoma, IDH-mutated, CNS5 WHO grade 4
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- Pregnancy or breastfeeding
- Significant known active cardiac disease within 6 months before enrollment, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
- Known hypersensitivity to any of the components of vorasidenib.
- 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.
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus 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 that is adequately suppressed by institutional practice will be permitted.
- Known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the gastrointestinal absorption of drugs administered orally.
- Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
- Inability or known contraindication to undergo contrast media MRI.
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial.
Trial locations and contacts
59 sites in 12 countries. Contact the study team or a site near you to ask about taking part.
59 sites in 12 countries
Canada16 sites, 16 recruiting
- Not yet recruiting
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2
- Not yet recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
- Not yet recruiting
QEII Health Sciences Centre Capital District Health Authority
Halifax, Nova Scotia, B3H 1V7
- Not yet recruiting
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
- Not yet recruiting
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
- Not yet recruiting
London Health Sciences Centre Research Inc.
London, Ontario, N6A 5W9
- Not yet recruiting
CHUM-Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 0A9
- Not yet recruiting
Montreal Neurological Institute and Hospital James Administration Building
Montreal, Quebec, H3A 2B4
- Not yet recruiting
CIUSSS NIM - Hôpital du Sacré-Cœur de Montréal
Montreal, Quebec, H4J 1C5
- Not yet recruiting
Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6
- Not yet recruiting
Hotel-Dieu de Quebec
Québec, Quebec, G1R 2J6
- Not yet recruiting
CIUSSS de l'Estrie - Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
- Recruiting
Odette Cancer Centre Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
- Recruiting
University Health Network Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
- Not yet recruiting
BC Cancer Agency - Vancouver
Vancouver, British Columbia, V5Z 4E6
- Recruiting
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia10 sites, 10 recruiting
- Not yet recruiting
Flinders Medical Centre / Southern Adelaide Local Health Network
Bedford Park, SA 5042
- Not yet recruiting
Chris O'Brien LifeHouse
Camperdown, NSW 2050
- Not yet recruiting
Austin Hospital
Heidelberg, VIC 3084
- Not yet recruiting
Royal Hobart Hospital
Hobart, TAS 7000
- Not yet recruiting
Liverpool Hospital
Liverpool, NSW 2170
- Not yet recruiting
Peter MacCallum Cancer Centre
Melbourne, VIC 3000
- Not yet recruiting
the Alfred hospital
Melbourne, VIC 3000
- Not yet recruiting
Sir Charles Gairdner Hospital
Nedlands, WA 6009
- Not yet recruiting
Royal North Shore Hospital
St Leonards, NSW 2065
- Recruiting
Princess Alexandra Hospital
Woolloongabba, QLD 4102
France5 sites, 5 recruiting
- Recruiting
Universitary hospital Bordeaux France
Bordeaux
- Recruiting
CHU Lyon - Hopital neurologique Pierre Wertheimer
Lyon
- Recruiting
Marseille APHM
Marseille
- Recruiting
Assistance Publique Hopitaux de Paris APHP - Sorbonne
Paris
- Recruiting
Oncopole Claudius Regaud, IUCT-Oncopole
Toulouse
Germany5 sites, 5 recruiting
- Recruiting
Universitaskliniken Bonn
Bonn
- Recruiting
University Hospital Frankfurt -Senckenberg Institute of Neurooncology
Frankfurt
- Recruiting
NNeurology department heidelberg
Heidelberg
- Recruiting
Mannheim University Hospital
Mannheim
- Recruiting
Universitaetsklinikum Regensburg
Regensburg
Italy4 sites, 4 recruiting
- Recruiting
Bellaria Hospital, IRCCS Istituto delle Scienze Neurologiche - AUSL di Bologna
Bologna
- Recruiting
Veneto Institute of Oncology
Padova
- Not yet recruiting
Sapienza University
Roma
- Recruiting
AOU Citta della Salute e della Scienza di Torino
Torino
United Kingdom4 sites, 4 recruiting
- Not yet recruiting
Queen Elizabeth Hospital Birmingham
Birmingham
- Recruiting
The Christie NHS Foundation Trust
Manchester
- Recruiting
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral
- Recruiting
Royal Marsden Hospital
Surrey Quays
Austria3 sites, 3 recruiting
- Recruiting
Medical University of Innsbruck
Innsbruck
- Recruiting
Kepler University Hospital - Neuromed campus
Linz
- Recruiting
Medical University of Vienna
Vienna
Belgium3 sites, 3 recruiting
- Recruiting
Universitair Ziekenhuis Brussel
Brussels
- Recruiting
Ghent University Hospital
Ghent
- Recruiting
U.Z. Leuven - Campus Gasthuisberg
Leuven
Netherlands3 sites, 3 recruiting
- Recruiting
Amsterdam UMC location VUMC
Amsterdam
- Recruiting
Academisch Ziekenhuis Maastricht
Maastricht
- Recruiting
Erasmus MC
Rotterdam
Spain3 sites, 3 recruiting
- Recruiting
Hospital de Sant Pau i La Santa Creu
Barcelona
- Recruiting
Vall de Hebron Hospital
Barcelona
- Recruiting
Hospital Universitario 12 de Octubre
Madrid
Switzerland2 sites, 2 recruiting
- Recruiting
University Hospital Basel
Basel
- Recruiting
University Hospital Zurich
Zurich
About this study
Official title: 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)
The main goal of VIGOR is to demonstrate that vorasidenib maintenance therapy improves locally assessed progression-free survival (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.
The primary endpoint is Progression-free survival (PFS), as assessed locally from the date of enrolment using the RANO 2.0 criteria.
In this a comparative, randomized (1:1), triple blinded, multicentre phase III superiority trial with one stopping rule for efficacy and futility after end of enrolment, participants in the experimental arm will receive vorasidenib orally once daily at a dose of 40 mg in continuous 28-day cycles while participants in the control arm will receive a matched oral placebo once daily in continuous 28-day cycles
Read the detailed description
Diffuse gliomas are the most common primary brain tumors in adults and are associated with high morbidity and mortality. Approximately 25% of diffuse gliomas harbour mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes. Among IDH-mutated gliomas, IDH-mutant astrocytoma is the most common diagnosis and occurs mainly in adults in their thirties or forties. Most cases correspond to CNS5 WHO grade 2 and 3, while grade 4 tumors are rare. The prognosis of grade 2 and 3 tumors is significantly better (median overall survival times up to 10 years) than that of grade 4 tumors (median overall survival times around 3-7 years).
According to international guidelines and based on randomized clinical trials, treatment options for IDH-mutated astrocytoma after maximum safe neurosurgical resection include active surveillance or radiotherapy followed by chemotherapy with procarbazine, lomustine and vincristine (PCV) or temozolomide. An active surveillance strategy, however, can be recommended for patients with oligodendroglioma grade 2 or astrocytoma grade 2 with particularly favourable prognostic factors, such as absence of neurological deficits and limited tumor burden. Despite this multimodal treatment, IDH-mutant astrocytomas recur and ultimately lead to patient death, with median progression-free survival times around 7 years and overall survival times of approximately 9-11 years. Novel treatment strategies are needed to extend the survival of these patients.
Recently, the international randomized placebo-controlled phase III INDIGO trial has shown considerable efficacy on progression free survival of the mutant IDH inhibitor vorasidenib in patients with IDH-mutant diffuse grade 2 gliomas that were considered candidates for an active surveillance strategy by the treating physician. Vorasidenib (AG881) is an orally available brain-penetrant dual inhibitor of mutant IDH1 and IDH2 proteins. INDIGO enrolled patients with residual or recurrent non-enhancing grade 2 IDH-mutant glioma who had not received prior radiotherapy or chemotherapy. Participants received either vorasidenib (40 mg once daily) or a matched placebo, given continuously in 28-day cycles. From January 2020 through February 2022, a total of 331 participants were randomly assigned to receive vorasidenib (168 participants) or placebo (163 participants ). The image-based progression-free survival was significantly longer for participants in the vorasidenib group than in the placebo group: 27.7 months (95% CI, 17.0 to non-estimable) vs 11.1 months (95% CI, 11.0-13.7), with a hazard-ratio for disease progression or death of 0.39 (95% CI, 0.27-0.56, p<0.001). Additionally, time to next intervention was significantly delayed in the vorasidenib group as compared to the placebo group with a hazard ratio of 0.26 (95% CI, 0.15-0.43, p<0.001). Adverse events leading to treatment interruption occurred in 3.6% of the vorasidenib group and 1.2% of the placebo group. An increased alanine amino transferase level of grade 3 or higher occurred in 9.6% of participants receiving vorasidenib and in none of the participants receiving placebo. Overall, based on the INDIGO trial data, registrational approval by the FDA was granted in August 2024 and EMA approval is expected. Vorasidenib is likely to enter routine clinical practice for patients with IDH-mutant gliomas that do not require immediate chemoradiotherapy.
In the current trial, the investigator will evaluate whether adding vorasidenib as maintenance therapy after completion of standard chemoradiotherapy in patients with astrocytoma, IDH-mutant, CNS5 WHO Grade 2 or 3 prolongs progression-free survival compared to placebo. This trial will also explore the effect of vorasidenib maintenance treatment on overall survival, response rate, time to next intervention, toxicity, health-related quality of life, neurological symptoms, and neurocognitive function. Additionally, this trial will enable translational research through the analysis of tissue samples, liquid biopsies (blood samples), and neuroimaging data.
Overall, VIGOR aims to establish a new standard of care for IDH-mutated, CNS5 WHO Grade 2 or 3 astrocytoma by incorporating maintenance targeted therapy with vorasidenib into the current standard of care chemoradiotherapy.
- Conditions
- IDH-mutant Grade 2 or 3 Astrocytoma
- Being tested
- Vorasidenib, Vorasidenib Placebo
- Keywords
- Astrocytoma, IDH-mutant grade 2 or 3, Vorasidenib, Placebo- controlled, Triple-blinded, Phase III study
- Medical subject headings
- Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorasidenibDrug
Vorasidinib will be administered orally once daily at a dose of 40 mg in continuous 28-day cycles
Vorasidenib PlaceboDrug
Matched oral vorasidenib placebo will be administered once daily in continuous 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | Participants will receive vorasidenib orally once daily at a dose of 40 mg in continuous 28-day cycles up to 5 years or until disease progression, unacceptable toxicity, or withdrawal of patient consent. Receives: Drug: Vorasidenib |
| Control arm | Placebo comparator | Participants will receive a matched oral vorasidenib placebo once daily in continuous 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of patient consent for up to 5 years. Receives: Drug: Vorasidenib Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) by local assessment
Progression-free survival (PFS) will be defined as the number of days from date of enrolment to the date of earliest disease progression based on Response Assessment (RANO 2.0) or to the date of death due to any cause, if disease progression did not occur (the date of progression or death or censoring - date of enrolment + 1).
Patients who received new anti-cancer therapy or cancer-related surgery or radiotherapy prior to progression or death will not be censored at the last assessment where the patient was documented as progression free prior to the new anti-cancer therapy or cancer-related surgery or radiotherapy, instead progression after start of new therapy or surgery will be considered a valid event for PFS.
Measured: ~7.7 years and 10.5 years from first patient in
Secondary outcomes (17)
PFS by local assessment
Progression-free survival (PFS) will be defined as the number of days from date of enrolment to the date of earliest disease progression based on Response Assessment (RANO 2.0) or to the date of death due to any cause, if disease progression did not occur (the date of progression or death or censoring - date of enrolment + 1).
Patients who received new anti-cancer therapy or cancer-related surgery or radiotherapy prior to progression or death will not be censored at the last assessment where the patient was documented as progression free prior to the new anti-cancer therapy or cancer-related surgery or radiotherapy, instead progression after start of new therapy or surgery will be considered a valid event for PFS.
Measured: ~7.7 years and 10.5 years from first patient in
Progression-free survival (PFS) from the start of radiotherapy
Progression-free survival from the start of radiotherapy will be defined as the number of days from date of start of radiotherapy till progression or censoring with the same rules as for PFS.
Measured: ~7.7 years and 10.5 years from first patient in
Overall Survival
Overall survival (OS) will be defined as the number of days from date of enrolment to the date of death due to any cause (the date of death or censoring - date of enrolment +1). If a subject has not died, the data will be censored at the last date documented to be alive. Patients still alive (or not known to have died before the cutoff date) or lost to follow-up are censored at the last date known to be alive.
Measured: ~7.7 years and 10.5 years from first patient in
Overall Response
All patients included in the study must be assessed for their overall response treatment based on RANO 2.0 criteria at each assessment of the disease, from the start of study treatment until disease progression , even if there is a major protocol treatment deviation, if they are ineligible, or not followed/ /re-evaluated.
Each patient will be assigned one of the following categories: complete response (CR), partial response (PR), minor response (MR, applicable only to non-enhancing disease), stable disease (SD), Equivocal progressive disease (EqPD), progressive disease (PD), early death (ED) or not evaluable (NE).
Early death is defined as any death occurring before the first per protocol time point of tumour re-evaluation.
Measured: ~7.7 years and 10.5 years from first patient in
Time to next intervention
Time to next intervention (TTNI) will be defined as the number of days calculated from the date of enrolment until the commencement of further anticancer treatment following vorasidenib or placebo discontinuation (including surgery or radiotherapy), irrespective of whether progression was documented. If a patient does not initiate further anticancer therapy TTNI will be censored at the date of death or last known alive date.
Measured: ~7.7 years and 10.5 years from first patient in
Adverse events
All adverse events (AEs) will be recorded; the investigator will assess whether those events are drug related (reasonable possibility, no reasonable possibility) and this assessment will be recorded in the database for all AEs.
The collection period for all AEs will start up to 4 weeks prior to enrolment and until 30 days after the end of treatment. After those 30 days, only SAEs related to study drug or study participation have to be collected.
All AEs must be followed until resolution or stabilization.
Measured: ~7.7 years from first patient in
Health-related Quality of Life QLQ-C30.
Health related quality of life (HRQoL) will be measured using a questionnaire which will be completed by the patient: EORTC QLQ-C30
Measured: ~7.7 years from first patient in
Health-related Quality of Life QLQ-BN20.
Health related quality of life (HRQoL) will be measured using a questionnaire which will be completed by the patient: EORTC QLQ-BN20.
Measured: ~7.7 years from first patient in
Health-related Quality of Life IADL-BN32
Health related quality of life (HRQoL) will be measured using a questionnaire which will be completed by the patient: IADL-BN32
Measured: ~7.7 years from first patient in
Health-related Quality of Life item list 46 (IL46)
Health related quality of life (HRQoL) will be measured using a questionnaire which will be completed by the patient: item list 46 (IL46)
Measured: ~7.7 years from first patient in
Neurocognitive function HVLT-R - Part A Free recall
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: HVLT-R - Part A Free recall
Measured: ~7.7 years from first patient in
Neurocognitive function TMT - Part A
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: TMT - Part A
Measured: ~7.7 years from first patient in
Neurocognitive function TMT - Part B
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: TMT - Part B
Measured: ~7.7 years from first patient in
Neurocognitive function COWA
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: COWA
Measured: ~7.7 years from first patient in
Neurocognitive function MOS scale
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: MOS scale
Measured: ~7.7 years from first patient in
Neurocognitive function HVLT-R - Part B Delayed recall HVLT-R - Part C Delayed recognition
Neurocognitive function will be measured using a questionnaire which will be completed by the patient: HVLT-R - Part B Delayed recall HVLT-R - Part C Delayed recognition
Measured: ~7.7 years from first patient in
Seizure activity
Seizure activity will be measured using will be measured using a questionnaire which will be completed by the physician: Seizure Control Composite Score Index
Measured: ~7.7 years from first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start16 Jan 2026
- Primary completion13 Apr 2035 (estimated)
- Study completion31 May 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for IDH-mutant Grade 2 or 3 AstrocytomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 468 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Canadian Cancer Trials Group, Olivia Newton-John Cancer Research Institute
- Responsible party
- Sponsor
- Investigators
- Matthias Preusser, Study chair, Universitaetsklinikum Wien - AKH uniklinieken, Vienna, Austria.Marjolein Geurts, Study chair, Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06809322
- Sponsor's protocol ID
- EORTC -2427-BTG
- Other IDs
- 2024-519404-27-00, CE.10
- Acronym
- VIGOR
- Status last verified
- Oct 2026
- First submitted
- 22 Jan 2025
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No