Clinical trial • Phase III • Oncology
VORASIDENIB for Grade 2 glioma (oligodendroglioma or astrocytoma) — residual or recurrent, IDH1 or IDH2 mutation
Phase III trial of VORASIDENIB for Grade 2 glioma (oligodendroglioma or astrocytoma) — residual or recurrent, IDH1 or IDH2 mutation.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Grade 2 glioma (oligodendroglioma or astrocytoma) — residual or recurrent, IDH1 or IDH2 mutation
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 14-06-2024
- First CTIS Authorization Date
- 15-07-2024
Trial design
Randomised, placebo (matched tablets) orally vs vorasidenib 40 mg qd (vorasidenib film-coated tablets; active arm: vorasidenib 40 mg qd, days 1–28 in 28-day cycles; placebo supplied as matched tablets administered orally).-controlled, crossover Phase III trial in France, Italy, Spain and others.
- Randomised
- Yes
- Comparator
- Placebo (matched tablets) orally vs vorasidenib 40 mg QD (vorasidenib film-coated tablets; active arm: vorasidenib 40 mg QD, Days 1–28 in 28-day cycles; placebo supplied as matched tablets administered orally).
- Crossover
- Yes
- Biomarker Stratified
- True (1p19q status; strata: co-deleted vs not co-deleted)
- Target Sample Size
- 269
- Trial Duration For Participant
- 1825
Stratification factors
- Local 1p19q status (co-deleted vs not co-deleted)
- Baseline tumor size per local assessment (longest diameter ≥2 cm vs <2 cm)
Eligibility
Recruits 269 paediatric patients.
- Vulnerable Population
- Vulnerable population selected: includes adolescents (minimum age 12 years). Age-appropriate consent/assent materials are provided (adolescent 12–17 ICFs and parental/guardian ICFs are available per country). Protocol uses LPPS for subjects <16 years and KPS for ≥16 years, indicating paediatric/adolescent-specific assessments and consent/assent handling.
Inclusion criteria
- {"criterion_text":"- 1. Be at least 12 years of age and weigh at least 40 kg.\n- 2. Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.\n- 3. Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy, and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.\n- 4. Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory.\n- 5. Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.\n- 6. Have a KPS score (for subjects ≥16 years of age) or LPPS score (for subjects <16 years of age) of ≥80%."}
Exclusion criteria
- {"criterion_text":"- 1. Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc.\n- 2. Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen)."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Radiographic PFS as assessed by the BIRC per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas [RANO-LGG]","definition_or_measurement_approach":"Radiographic progression-free survival assessed by the blinded independent review committee (BIRC) using the modified RANO-LGG criteria."}
Secondary endpoints
- {"endpoint_text":"- 1. The key secondary endpoint is TTNI.","definition_or_measurement_approach":"Time to next intervention (TTNI) compared between vorasidenib and placebo."}
- {"endpoint_text":"- 2.Other secondary efficacy endpoints are TGR, objective response, CR+PR, time to response, time to CR+PR, duration of response, duration of CR+PR, OS, FACT-BR scores, and PFS by investigator.","definition_or_measurement_approach":"Tumor growth rate (TGR) by volume per BIRC; objective response (CR+PR), time to response, time to CR+PR, duration of response/CR+PR assessed by BIRC and Investigator; overall survival (OS); health-related quality of life by FACT-Br; PFS per investigator assessment."}
- {"endpoint_text":"- 3. Adverse events, serious adverse events (SAEs), and AEs leading to discontinuation or death, and severity of AEs","definition_or_measurement_approach":"Safety endpoints include incidence and severity of AEs, SAEs, and AEs leading to discontinuation or death (standard AE reporting)."}
- {"endpoint_text":"- 4. Safety laboratory parameters, vital signs, 12-lead electrocardiograms (ECGs), evaluation of left ventricular ejection fraction (LVEF), Karnofsky Performance Scale (KPS)/Lansky Play-Performance Scale (LPPS), and concomitant medications.","definition_or_measurement_approach":"Clinical safety assessments including labs, vitals, ECGs, LVEF evaluation, performance scales (KPS/LPPS), and concomitant medication review."}
- {"endpoint_text":"- 5. Serial or sparse blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters of vorasidenib and its circulating metabolite AGI-69460.","definition_or_measurement_approach":"Pharmacokinetic sampling (serial or sparse) to determine plasma concentration–time profiles and PK parameters for vorasidenib and metabolite AGI-69460."}
Recruitment
- Planned Sample Size
- 269
- Recruitment Window Months
- 98
- Consent Approach
- Informed consent obtained using country/language-specific main ICFs for adults. For adolescents (12–17) separate adolescent ICFs and parental/guardian ICFs are provided (documents available in multiple languages). ICFs and related materials available in English, French, Spanish, Italian, Dutch and German as per country-specific documentation.
Geography
- Total Number Of Sites
- 16
- Total Number Of Participants
- 71
France
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 22-07-2024
- Processing Time Days
- 14
- Number Of Sites
- 3
- Number Of Participants
- 32
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Service de Neurologie Vasculaire
- Principal Investigator Name
- François Ducray
- Principal Investigator Email
- francois.ducray@chu-lyon.fr
- Contact Person Name
- François Ducray
- Contact Person Email
- francois.ducray@chu-lyon.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Neurologie 2- Batiment Mazarin
- Principal Investigator Name
- Mehdi Touat
- Principal Investigator Email
- mehdi.touat@gmail.com
- Contact Person Name
- Mehdi Touat
- Contact Person Email
- mehdi.touat@gmail.com
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Neuro-Oncology
- Principal Investigator Name
- Olivier-Louis Chinot
- Principal Investigator Email
- olivier.chinot@ap-hm.fr
- Contact Person Name
- Olivier-Louis Chinot
- Contact Person Email
- olivier.chinot@ap-hm.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 22-07-2024
- Processing Time Days
- 14
- Number Of Sites
- 4
- Number Of Participants
- 10
Sites
- Site Name
- Istituto Oncologico Veneto
- Department Name
- S.C. Oncologia 1
- Principal Investigator Name
- Giuseppe Lombardi
- Principal Investigator Email
- giuseppe.lombardi@iov.veneto.it
- Contact Person Name
- Giuseppe Lombardi
- Contact Person Email
- giuseppe.lombardi@iov.veneto.it
- Site Name
- Humanitas Mirasole S.p.A.
- Department Name
- U.O di Oncologia ed Ematologia
- Principal Investigator Name
- Matteo Simonelli
- Principal Investigator Email
- matteo.simonelli@hunimed.eu
- Contact Person Name
- Matteo Simonelli
- Contact Person Email
- matteo.simonelli@hunimed.eu
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- SSD Neuro-oncologia Clinica
- Principal Investigator Name
- Alessia Pellerino
- Principal Investigator Email
- alessia.pellerino85@gmail.com
- Contact Person Name
- Alessia Pellerino
- Contact Person Email
- alessia.pellerino85@gmail.com
- Site Name
- Azienda Unita Sanitaria Locale Di Bologna
- Department Name
- UOC Oncologia del Sistema Nervoso
- Principal Investigator Name
- Enrico Franceschi
- Principal Investigator Email
- e.franceschi@isnb.it
- Contact Person Name
- Enrico Franceschi
- Contact Person Email
- e.franceschi@isnb.it
Spain
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 17-07-2024
- Processing Time Days
- 9
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncology
- Principal Investigator Name
- Juan Manuel Sepúlveda Sanchez
- Principal Investigator Email
- sepulvedasanchez@seom.org
- Contact Person Name
- Juan Manuel Sepúlveda Sanchez
- Contact Person Email
- sepulvedasanchez@seom.org
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Oncology
- Principal Investigator Name
- María Ángeles Vaz Salgado
- Principal Investigator Email
- mavaz4@gmail.com
- Contact Person Name
- María Ángeles Vaz Salgado
- Contact Person Email
- mavaz4@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Principal Investigator Name
- Maria Vieito Villar
- Principal Investigator Email
- mvieito@vhio.net
- Contact Person Name
- Maria Vieito Villar
- Contact Person Email
- mvieito@vhio.net
Netherlands
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 15-07-2024
- Processing Time Days
- 7
- Number Of Sites
- 2
- Number Of Participants
- 10
Sites
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Dept. of Medical Oncology
- Principal Investigator Name
- Filip De Vos
- Principal Investigator Email
- f.devos@umcutrecht.nl
- Contact Person Name
- Filip De Vos
- Contact Person Email
- f.devos@umcutrecht.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Neurology
- Principal Investigator Name
- Jacoline Bromberg
- Principal Investigator Email
- j.bromberg@erasmusmc.nl
- Contact Person Name
- Jacoline Bromberg
- Contact Person Email
- j.bromberg@erasmusmc.nl
Germany
- Earliest CTIS Part Ii Submission Date
- 08-07-2024
- Latest Decision Or Authorization Date
- 22-07-2024
- Processing Time Days
- 14
- Number Of Sites
- 4
- Number Of Participants
- 9
Sites
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Klinik für Neurochirurgie
- Principal Investigator Name
- Frank Lennard Ricklefs
- Principal Investigator Email
- f.ricklefs@uke.de
- Contact Person Name
- Frank Lennard Ricklefs
- Contact Person Email
- f.ricklefs@uke.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Abteilung Klinische Neuroonkologie Klinik für Neurologie
- Principal Investigator Name
- Sied Kebir
- Principal Investigator Email
- Sied.Kebir@uk-essen.de
- Contact Person Name
- Sied Kebir
- Contact Person Email
- Sied.Kebir@uk-essen.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Neurologische Klinik
- Principal Investigator Name
- Wolfgang Wick
- Principal Investigator Email
- Wolfgang.Wick@med.uni-heidelberg.de
- Contact Person Name
- Wolfgang Wick
- Contact Person Email
- Wolfgang.Wick@med.uni-heidelberg.de
- Site Name
- Universitat Heidelberg (Medizinische Fakultät Mannheim der Universität Heidelberg)
- Department Name
- Medizinische Fakultät Mannheim der Universität Heidelberg
- Principal Investigator Name
- Michael Platten
- Principal Investigator Email
- michael.platten@umm.de
- Contact Person Name
- Michael Platten
- Contact Person Email
- michael.platten@umm.de
Sponsor
Primary sponsor
- Full Name
- Institut De Recherches Internationales Servier IRIS
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- France
Contract research organisations
- Name
- PPD Development LP
- Responsibilities
- SUSAR reporting, regulatory activities and multiple clinical trial support functions
- Name
- Ppd Inc.
- Responsibilities
- PK samples analysis
- Name
- Fortrea Inc.
- Responsibilities
- Statistical programming support for ADaM and TFL generation
- Name
- Endpoint Clinical Inc.
- Responsibilities
- IMP dispensation and inventory management, IVRS and treatment randomisation
- Name
- Almac Clinical Services LLC
- Responsibilities
- Packaging, labeling, QP release and distribution of the IMP
Third parties
- {"country":"United States","full_name":"Life Technologies Clinical Services Lab Inc.","duties_or_roles":"Analysis of pre-screening tumor samples for confirmation of presence of IDH1 and/or IDH2 mutation","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Meeting Protocol Worldwide LP","duties_or_roles":"Planning and execution of US Investigator Meeting","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Xogene Services LLC","duties_or_roles":"Clinical data registry posting support","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Cogstate Inc.","duties_or_roles":"Provide ePRO tablets and Cogstate eSource Platform to administer the Cogstate Battery of Tests","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Statistical programming support for generating ADaM and TFLs for planned and ad-hoc analysis","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"URL, Project Support and EDC hosting services","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"PK samples analysis","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"SUSAR Reporting and Regulatory Activities; other clinical supply and reporting responsibilities","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IMP dispensation and inventory management, IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Drugdev Inc.","duties_or_roles":"Site Payments","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"Electronic platform for administration of questionnaires: EQ-5D-5L; PGI-C; FACT-Br","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Rxlogix Corp.","duties_or_roles":"Hosting and managed services provider of Argus Safety Database & PV Analytics Suite","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medqia LLC","duties_or_roles":"Blinded Independent Review Committee (BIRC) for collection and central read of MRI scans","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Coagulation, pregnancy testing (serum), support with lab kit supply and management of samples","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Packaging, labeling, QP release, and distribution of the IMP","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- S95032/AG-881
- Active Substance
- VORASIDENIB
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- MIA numbers provided: IMP12181/00001/ DE_NW_05_MIA_2020_0002 / UK MIA 20377
- Starting Dose
- 40 mg
- Dose Levels
- 10 mg; 40 mg
- Frequency
- Once daily (QD)
- Maximum Dose
- 40 mg/day
- Investigational Product Name
- Placebo tablets to match S95032 drug product
- Modality
- Other
- Routes Of Administration
- Oral
- Route
- Oral
- Dose Levels
- Matched 10 mg and 40 mg tablet presentations
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