Vorasidenib: Vorasidinib will be administered orally once daily at a dose of 40 mg in continuous 28-day cycles
Vorasidenib Placebo: Matched oral vorasidenib placebo will be administered once daily in continuous 28-day cycles
Study 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.
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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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).
* 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.
Exclusion Criteria:
* 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
* 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.
Primary outcome measure(s)
Progression-free survival (PFS) by local assessment — ~7.7 years and 10.5 years from first patient in 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.
Trial sites (59)
Facility
City
Region
Status
Flinders Medical Centre / Southern Adelaide Local Health Network
Bedford Park
Australia
Not Yet Recruiting
Chris O'Brien LifeHouse
Camperdown
Australia
Not Yet Recruiting
Austin Hospital
Heidelberg
Australia
Not Yet Recruiting
Royal Hobart Hospital
Hobart
Australia
Not Yet Recruiting
Liverpool Hospital
Liverpool
Australia
Not Yet Recruiting
Peter MacCallum Cancer Centre
Melbourne
Australia
Not Yet Recruiting
the Alfred hospital
Melbourne
Australia
Not Yet Recruiting
Sir Charles Gairdner Hospital
Nedlands
Australia
Not Yet Recruiting
Royal North Shore Hospital
St Leonards
Australia
Not Yet Recruiting
Princess Alexandra Hospital
Woolloongabba
Australia
Recruiting
Medical University of Innsbruck
Innsbruck
Austria
Recruiting
Kepler University Hospital - Neuromed campus
Linz
Austria
Recruiting
Medical University of Vienna
Vienna
Austria
Recruiting
Universitair Ziekenhuis Brussel
Brussels
Belgium
Recruiting
Ghent University Hospital
Ghent
Belgium
Recruiting
U.Z. Leuven - Campus Gasthuisberg
Leuven
Belgium
Recruiting
Arthur J.E. Child Comprehensive Cancer Centre
Calgary
Alberta
Not Yet Recruiting
Cross Cancer Institute
Edmonton
Alberta
Not Yet Recruiting
BC Cancer Agency - Vancouver
Vancouver
British Columbia
Not Yet Recruiting
CancerCare Manitoba
Winnipeg
Manitoba
Recruiting
QEII Health Sciences Centre Capital District Health Authority
Halifax
Nova Scotia
Not Yet Recruiting
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton
Ontario
Not Yet Recruiting
Kingston Health Sciences Centre
Kingston
Ontario
Not Yet Recruiting
London Health Sciences Centre Research Inc.
London
Ontario
Not Yet Recruiting
Ottawa Hospital Research Institute
Ottawa
Ontario
Not Yet Recruiting
Odette Cancer Centre Sunnybrook Health Sciences Centre
Toronto
Ontario
Not Yet Recruiting
University Health Network Princess Margaret Cancer Centre
Toronto
Ontario
Not Yet Recruiting
CHUM-Centre Hospitalier de l'Universite de Montreal
Montreal
Quebec
Not Yet Recruiting
Montreal Neurological Institute and Hospital James Administration Building
Montreal
Quebec
Not Yet Recruiting
CIUSSS NIM - Hôpital du Sacré-Cœur de Montréal
Montreal
Quebec
Not Yet Recruiting
Hotel-Dieu de Quebec
Québec
Quebec
Not Yet Recruiting
CIUSSS de l'Estrie - Centre hospitalier universitaire de Sherbrooke
Sherbrooke
Quebec
Not Yet Recruiting
Masaryk Memorial Cancer Institute
Brno
Czechia
Recruiting
Universitary hospital Bordeaux France
Bordeaux
France
Recruiting
CHU Lyon - Hopital neurologique Pierre Wertheimer
Lyon
France
Recruiting
Marseille APHM
Marseille
France
Recruiting
Assistance Publique Hopitaux de Paris APHP - Sorbonne
Paris
France
Recruiting
Oncopole Claudius Regaud, IUCT-Oncopole
Toulouse
France
Recruiting
Universitaskliniken Bonn
Bonn
Germany
Recruiting
University Hospital Frankfurt -Senckenberg Institute of Neurooncology
Frankfurt
Germany
Recruiting
+ 19 more sites — see the full list on the official registry below.
More European Organisation for Research and Treatment of Cancer - EORTC trials in Germany
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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