Clinical trial • Phase III • Oncology

IVOSIDENIB for Conventional chondrosarcoma (locally advanced or metastatic) with IDH1 mutation

Phase III trial of IVOSIDENIB for Conventional chondrosarcoma (locally advanced or metastatic) with IDH1 mutation.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Conventional chondrosarcoma (locally advanced or metastatic) with IDH1 mutation
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
15-02-2024
First CTIS Authorization Date
10-06-2024

Trial design

Randomised, ivosidenib 500 mg orally once daily (two 250 mg tablets once daily) versus matching placebo tablets taken orally once daily-controlled Phase III trial in Denmark, Belgium, Italy and others.

Randomised
Yes
Comparator
Ivosidenib 500 mg orally once daily (two 250 mg tablets once daily) versus matching placebo tablets taken orally once daily
Target Sample Size
106
Trial Duration For Participant
730

Eligibility

Recruits 106 Vulnerable population selected. Informed consent is obtained using L1_SIS and ICF Main and Pre-screening forms (and Pregnant Partner ICFs where applicable). eCONSENT/eCOA is provided via Medable (third party responsible for eCOA/eCONSENT). Participant information and consent documents are available in multiple languages as per documentation..

Pregnancy Exclusion
Pregnant or lactating women.
Vulnerable Population
Vulnerable population selected. Informed consent is obtained using L1_SIS and ICF Main and Pre-screening forms (and Pregnant Partner ICFs where applicable). eCONSENT/eCOA is provided via Medable (third party responsible for eCOA/eCONSENT). Participant information and consent documents are available in multiple languages as per documentation.

Inclusion criteria

  • {"criterion_text":"- Have a histopathological diagnosis consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection or other local therapeutic options as per standard of care such as definitive radiotherapy for skull base lesions.\n- Have at least one BICR-confirmed measurable lesion as defined by RECIST v1.1. Participants who have received prior radiation therapy are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ≥20% growth in size since post-treatment assessment.\n- Have received 0 to 2 prior systemic treatment regimens in the advanced/metastatic setting for chondrosarcoma.\n- Have radiographic progression/recurrence of disease according to RECIST v1.1 defined as: - Radiographic progression of disease (local and/or distant) documented by 2 imaging assessments performed no more than 6 months (+3 weeks) apart within 12 months before randomization. OR - Any recurrence of disease (local and/or distant) after complete surgical resection and documented by imaging within 6 months (+3 weeks) before randomization.\n- Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or banked tumor tissue available that was sourced from either a primary or metastatic tumor lesion) based on central laboratory testing (R132C/L/G/H/S mutation variants)\n- Have recovered from any clinically relevant sequelae and toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer."}

Exclusion criteria

  • {"criterion_text":"- Are unable to swallow oral medication.\n- Pregnant or lactating women.\n- Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed.\n- Have received prior therapy with an IDH1 inhibitor\n- Have received systemic anticancer therapy <2 weeks prior to randomization (for investigational or immune-based anticancer therapy <4 weeks).\n- Have received radiotherapy <2 weeks prior to randomization.\n- Have known symptomatic brain metastases requiring steroids >10 mg per day prednisone (or equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued or reduced corticosteroid treatment <=10 mg per day for these metastases for at least 4 weeks and have radiographically stable disease of brain lesions for at least 3 months prior to randomization.\n- Have a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated carcinoma in situ; or c) pT1-2 prostatic cancer Gleason score ≤6 or d) participant is free of other primary solid or liquid tumor for ≥ 1 year prior to the start of study treatment and, in the opinion of the Investigator, the disease will not affect participant's outcome in the setting of current chondrosarcoma diagnosis.\n- Have had major surgery within 4 weeks prior to randomization.\n- Have significant active cardiac disease within 6 months prior to randomization, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction; unstable angina; and/or stroke.\n- Have LVEF <40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to randomization.\n- Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome, familial history of sudden death or polymorphic ventricular arrhythmia). Participants with a bundle branch block combined with a prolonged QTcF interval may be permitted based on local cardiology assessment.\n- Have known medical history of progressive multifocal leukoencephalopathy (PML)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants","definition_or_measurement_approach":"Assessed by a Blinded Independent Central Reviewer (BICR) based on tumor assessments (tumor measurements as per study imaging schedule; RECIST v1.1 referenced elsewhere for measurable disease definition)."}

Secondary endpoints

  • {"endpoint_text":"- PFS based on BICR assessment in all randomized participants","definition_or_measurement_approach":"Assessed by BICR (tumor assessments)."}
  • {"endpoint_text":"- Overall survival (OS) in Grade 1 and Grade 2 participants","definition_or_measurement_approach":"Overall Survival (OS) measured as stated in protocol (time-to-event endpoint capturing death; specific analysis details in protocol)."}
  • {"endpoint_text":"- OS in all randomized participants","definition_or_measurement_approach":"Overall Survival (OS) measured as stated in protocol."}
  • {"endpoint_text":"- PFS based on Investigator assessment in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Investigator-assessed PFS (tumor assessments by local investigator, per protocol)."}
  • {"endpoint_text":"- Objective response (OR) (complete response(CR) or partial response (PR)) of anti-tumor activity (using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Objective response per RECIST v1.1 (CR or PR assessed on imaging)."}
  • {"endpoint_text":"- Duration of response (DOR) in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Duration of response per RECIST v1.1 definitions (time from first documented response to progression or death)."}
  • {"endpoint_text":"- Time to response (TTR) in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Time to response as defined in protocol (time from randomization to first documented response)."}
  • {"endpoint_text":"- Disease control (DC) CR, PR, or stable disease (SD)) in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Disease control defined as CR, PR or SD according to RECIST v1.1."}
  • {"endpoint_text":"- Duration of disease control (DoDC) in Grade 1 and Grade 2 participants and in all randomised participants","definition_or_measurement_approach":"Duration of disease control per protocol (time from documentation of disease control to progression or death)."}
  • {"endpoint_text":"- Number of Adverse Events (AEs), Number of Serious Adverse Events (SAEs), Number of Adverse Events of Special Interest (AESIs), Number of Adverse Events (AEs) leading to discontinuation, treatment interruption, and dose reduction","definition_or_measurement_approach":"Safety endpoints captured as counts of AEs, SAEs, AESIs and events leading to discontinuation/interruption/dose reduction as recorded in safety reporting."}
  • {"endpoint_text":"- European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score","definition_or_measurement_approach":"Patient-reported HRQoL measured using the EORTC QLQ-C30 questionnaire."}
  • {"endpoint_text":"- European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score","definition_or_measurement_approach":"Patient-reported HRQoL measured using EQ-5D-5L instrument."}
  • {"endpoint_text":"- Patient-Reported Outcomes Measurement Information System (PROMIS) score","definition_or_measurement_approach":"Patient-reported outcomes measured using PROMIS instruments."}
  • {"endpoint_text":"- Ivosidenib and 2-hydroxyglutarate (2-HG) concentration in plasma","definition_or_measurement_approach":"Pharmacokinetic (ivosidenib) and pharmacodynamic (2-HG) plasma concentrations measured from plasma samples (central laboratory analyses)."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
106
Recruitment Window Months
83
Consent Approach
Informed consent obtained from adult participants (≥18) using L1_SIS and ICF Main and Pre-screening forms; specific Pregnant Partner ICFs exist. eConsent (eCONSENT/eCOA) is provided via Medable (third party). Consent and patient-facing documents are provided in multiple languages (English, French, German, Italian, Dutch, Spanish and others as per documentation).

Methods

  • Study website / Basic Website patient-facing copy (K1_CHONQUER_Basic Website documents)
  • Patient advertisements including video scripts (K2_Patient Advertisement and video script documents)
  • Site-level recruitment via participating hospitals/oncology clinics (local site referrals and contacts at listed trial sites)
  • Study website and patient-facing materials managed/hosted by third party (Clariness indicated as responsible for Study website)

Geography

Total Number Of Sites
40
Total Number Of Participants
50

Denmark

Earliest CTIS Part Ii Submission Date
07-08-2025
Latest Decision Or Authorization Date
12-08-2025
Processing Time Days
5
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Region Midtjylland
Department Name
Department of Oncology
Contact Person Name
Philip Blach Rossen
Contact Person Email
philross@rm.dk
Site Name
Region Hovedstaden
Department Name
Department of Oncology
Contact Person Name
Bodil Elisabeth Engelmann

Belgium

Earliest CTIS Part Ii Submission Date
04-07-2025
Latest Decision Or Authorization Date
24-07-2025
Processing Time Days
20
Number Of Sites
3
Number Of Participants
2

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
Medical Oncology
Contact Person Name
Filomena Mazzeo
Site Name
Universitair Ziekenhuis Gent
Department Name
Poli Dagkliniek, Medische Oncologie
Contact Person Name
Lore Lapeire
Contact Person Email
lore.lapeire@uzgent.be
Site Name
Centre hospitalier universitaire de Liege
Department Name
Medical Oncology
Contact Person Name
Christine Gennigens

Italy

Earliest CTIS Part Ii Submission Date
27-05-2024
Latest Decision Or Authorization Date
11-06-2024
Processing Time Days
15
Number Of Sites
8
Number Of Participants
10

Sites

Site Name
Azienda USL Toscana Centro
Department Name
S.O.C Medical Oncology
Contact Person Name
Giacomo Giulio Baldi
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Medical Oncology
Contact Person Name
Virginia Ferraresi
Contact Person Email
virginia.ferraresi@ifo.it
Site Name
Istituto Ortopedico Rizzoli
Department Name
SC Osteoncologia, Sarcomi dell'Osso e dei tessuti Molli e Terapia Innovativa
Contact Person Name
Giorgio Frega
Contact Person Email
giorgio.frega@ior.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
Oncology Operational Unit
Contact Person Name
Giuseppe Badalamenti
Contact Person Email
giuseppe.badalamenti@unipa.it
Site Name
Istituto Oncologico Veneto
Department Name
Oncology Department
Contact Person Name
Antonella Brunello
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Medical Oncology
Contact Person Name
Silvia Stacchiotti
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Oncology Department
Contact Person Name
Lorenzo D'Ambrosio
Contact Person Email
lorenzo.dambrosio@unito.it
Site Name
Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
Department Name
UOS DH Oncologico
Contact Person Name
Bruno Vincenzi

Germany

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-06-2024
Processing Time Days
19
Number Of Sites
8
Number Of Participants
9

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hematology, Oncology, and Tumor Immunology
Contact Person Name
Anne Flörcken
Contact Person Email
anne.floercken@charite.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Internal Medicine III
Contact Person Name
Verena Gaidzik
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Internal Medicine III
Contact Person Name
Lars Lindner
Site Name
HELIOS Klinikum Bad Saarow GmbH
Department Name
Oncology and Palliative Care
Contact Person Name
Daniel Pink
Site Name
Universitaet Muenster
Department Name
Medical Clinic and polyclinic A
Contact Person Name
Torsten Keßler
Contact Person Email
torsten.kessler@ukmuenster.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Medical Clinic and Polyclinic II
Contact Person Name
Jana Striefler
Contact Person Email
j.striefler@uke.de
Site Name
Universitat Heidelberg (Mannheim Cancer Center (MCC))
Department Name
Mannheim Cancer Center (MCC)
Contact Person Name
Bernd Kasper
Site Name
Technische Universitaet Dresden
Department Name
Medical Clinic and Polyclinic I
Contact Person Name
Stephan Richter

France

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
17-06-2024
Processing Time Days
25
Number Of Sites
9
Number Of Participants
10

Sites

Site Name
Institut Gustave Roussy
Department Name
Drug Development Department/Sarcoma Tumor Board
Contact Person Name
Benjamin VERRET
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service de cancerologie
Contact Person Name
Camille TLEMSANI
Contact Person Email
camille.tlemsani@aphp.fr
Site Name
Centre Oscar Lambret
Department Name
Oncologie Medicale
Contact Person Name
Thomas RYCKEWAERT
Contact Person Email
t-ryckewaert@o-lambret.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncologie Medicale
Contact Person Name
Justine GANTZER
Site Name
Centre Leon Berard
Department Name
Oncologie Medicale
Contact Person Name
Jean-Yves BLAY
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie Médicale
Contact Person Name
Emmanuelle BOMPAS
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Centre d'Essais Precoces en Cancerologie de Marseille (CEPCM)
Contact Person Name
Florence DUFFAUD
Contact Person Email
Florence.DUFFAUD@ap-hm.fr
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Oncologie Medicale
Contact Person Name
Thibaud VALENTIN
Site Name
Institut Bergonie
Department Name
Oncologie Medicale
Contact Person Name
Antoine ITALIANO

Netherlands

Earliest CTIS Part Ii Submission Date
27-02-2024
Latest Decision Or Authorization Date
17-06-2024
Processing Time Days
111
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Stichting Radboud University Medical Center
Department Name
Department of medical oncology
Contact Person Name
Ingrid Desar
Contact Person Email
ingrid.desar@radboudumc.nl
Site Name
Universitair Medisch Centrum Groningen
Department Name
Department of medical oncology
Contact Person Name
Jacco de Haan
Contact Person Email
j.j.de.haan@umcg.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Department of oncology
Contact Person Name
Hans Gelderblom
Contact Person Email
A.J.Gelderblom@lumc.nl

Spain

Earliest CTIS Part Ii Submission Date
27-05-2024
Latest Decision Or Authorization Date
10-06-2024
Processing Time Days
14
Number Of Sites
7
Number Of Participants
12

Sites

Site Name
Institut Catala D'oncologia
Department Name
Medical Oncology
Contact Person Name
Laura Jimenez Colomo
Contact Person Email
ljcolomo@iconcologia.net
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Medical Oncology
Contact Person Name
Roberto Diaz Beveridge
Contact Person Email
diaz_rob@gva.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Medical Oncology
Contact Person Name
Rosa Alvarez Alvarez
Contact Person Email
rosa.alvarez.al@gmail.com
Site Name
Hospital Universitario La Paz
Department Name
Medical Oncology
Contact Person Name
Andres Redondo Sanchez
Contact Person Email
andres.redondos@uam.es
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Medical Oncology
Contact Person Name
Javier Martin Broto
Contact Person Email
jmartin@atbsarc.org
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Medical Oncology
Contact Person Name
Raul Teres Lleida
Contact Person Email
RTeres@santpau.cat
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Contact Person Name
Claudia Maria Valverde Morales
Contact Person Email
cvalverde@vhio.net

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 Inc.
Responsibilities
PK/PD, 2-HG and study drug in plasma
Name
PPD Global Central Labs
Responsibilities
Central lab/Logistic platform
Name
IQVIA Limited
Responsibilities
biometrics

Third parties

  • {"country":"United States","full_name":"Thermo Fisher Scientific Inc.","duties_or_roles":"IDH1 mutation assessment","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"PK/PD, 2-HG and study drug in plasma","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central lab/Logistic platform","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"4Clinics","duties_or_roles":"Independent statistical center for Independent Data Monitoring Committee (IDMC)","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"biometrics","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"Study website","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"France","full_name":"Median Technologies","duties_or_roles":"Blinded Independant Central Reviewer of Imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"eCOA/ eCONSENT","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"France","full_name":"Firalis","duties_or_roles":"WES (Whole Exome Sequencing) analysis of buccal swab (germ-line mutations for control) and tumor biopsies","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long Term Storage / Biobank","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
AG-120/S95031 250mg film-coated tablet
Active Substance
IVOSIDENIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
oral
Starting Dose
500 mg once daily (two 250 mg tablets once daily)
Dose Levels
500 mg
Frequency
once daily
Maximum Dose
500 mg
Investigational Product Name
Ivosidenib-matched Placebo Tablets
Modality
Other

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