Vorasidenib Maintenance for IDH Mutant Astrocytoma

NCT06809322 | Recruiting Phase 3 DMC

• 3 other identifiers: EORTC -2427-BTG2024-519404-27-00CE.10
• Study Type: interventional
• Target: 468
• Locations: 11 countries
• Sites: 56

Brief 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

Conditions

IDH-mutant Grade 2 or 3 Astrocytoma

Keywords

Astrocytoma; IDH-mutant grade 2 or 3; Vorasidenib; Placebo- controlled; Triple-blinded; Phase III study

Outcome Measures

Primary Outcomes (1)

• 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.

  ~7.7 years and 10.5 years from first patient in

Secondary Outcomes (17)

• PFS by local assessment

  ~7.7 years and 10.5 years from first patient in

• Progression-free survival (PFS) from the start of radiotherapy

  ~7.7 years and 10.5 years from first patient in

• Overall Survival

  ~7.7 years and 10.5 years from first patient in

• Overall Response

  ~7.7 years and 10.5 years from first patient in

• Time to next intervention

  ~7.7 years and 10.5 years from first patient in

Study Arms (2)

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.

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.

Drug: Vorasidenib Placebo

Interventions

Vorasidenib DRUG

Vorasidinib will be administered orally once daily at a dose of 40 mg in continuous 28-day cycles

Experimental arm

Vorasidenib Placebo DRUG

Matched oral vorasidenib placebo will be administered once daily in continuous 28-day cycles

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: collaborator
• Olivia Newton-John Cancer Research Institute: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (59)

Flinders Medical Centre / Southern Adelaide Local Health Network

Bedford Park, SA 5042, Australia

NOT YET RECRUITING

Chris O'Brien LifeHouse

Camperdown, NSW 2050, Australia

NOT YET RECRUITING

Austin Hospital

Heidelberg, VIC 3084, Australia

NOT YET RECRUITING

Royal Hobart Hospital

Hobart, TAS 7000, Australia

NOT YET RECRUITING

Liverpool Hospital

Liverpool, NSW 2170, Australia

NOT YET RECRUITING

Peter MacCallum Cancer Centre

Melbourne, VIC 3000, Australia

NOT YET RECRUITING

the Alfred hospital

Melbourne, VIC 3000, Australia

NOT YET RECRUITING

Sir Charles Gairdner Hospital

Nedlands, WA 6009, Australia

NOT YET RECRUITING

Royal North Shore Hospital

St Leonards, NSW 2065, Australia

NOT YET RECRUITING

Princess Alexandra Hospital

Woolloongabba, QLD 4102, 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, T2N 5G2, Canada

NOT YET RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

NOT YET RECRUITING

BC Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

NOT YET RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

QEII Health Sciences Centre Capital District Health Authority

Halifax, Nova Scotia, B3H 1V7, Canada

NOT YET RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

NOT YET RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

NOT YET RECRUITING

London Health Sciences Centre Research Inc.

London, Ontario, N6A 5W9, Canada

NOT YET RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

NOT YET RECRUITING

Odette Cancer Centre Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

NOT YET RECRUITING

University Health Network Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

NOT YET RECRUITING

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

NOT YET RECRUITING

Montreal Neurological Institute and Hospital James Administration Building

Montreal, Quebec, H3A 2B4, Canada

NOT YET RECRUITING

CIUSSS NIM - Hôpital du Sacré-Cœur de Montréal

Montreal, Quebec, H4J 1C5, Canada

NOT YET RECRUITING

Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

NOT YET RECRUITING

CIUSSS de l'Estrie - Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

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

NNeurology department heidelberg

Heidelberg, Germany

RECRUITING

Mannheim University Hospital

Mannheim, Germany

RECRUITING

Universitaetsklinikum Regensburg

Regensburg, Germany

RECRUITING

Bellaria Hospital, IRCCS Istituto delle Scienze Neurologiche - AUSL di Bologna

Bologna, Italy

RECRUITING

Veneto Institute of Oncology

Padova, Italy

RECRUITING

Sapienza University

Roma, Italy

NOT YET RECRUITING

AOU Citta della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

Amsterdam UMC location VUMC

Amsterdam, Netherlands

RECRUITING

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

RECRUITING

Erasmus MC

Rotterdam, Netherlands

RECRUITING

Hospital de Sant Pau i La Santa Creu

Barcelona, Spain

RECRUITING

Vall de Hebron Hospital

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

University Hospital Basel

Basel, Switzerland

RECRUITING

University Hospital Zurich

Zurich, Switzerland

RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom

NOT YET RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

NOT YET RECRUITING

Royal Marsden Hospital

Surrey Quays, United Kingdom

RECRUITING

MeSH Terms

Conditions

Astrocytoma

Interventions

vorasidenib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Matthias Preusser

  Universitaetsklinikum Wien - AKH uniklinieken, Vienna, Austria.

  STUDY CHAIR

• Marjolein Geurts

  Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

  STUDY CHAIR

Central Study Contacts

EORTC HQ

CONTACT

+32 2 774611; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 5, 2025
• Study Start: January 16, 2026
• Primary Completion (Estimated): April 13, 2035
• Study Completion (Estimated): May 31, 2037
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

GB (4); IT (4); CZ (1); NL (3); BE (3); CH (2); DE (5); AU (10); FR (5); ES (3); CA (16)