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NCT06127407PHASE3Recruiting

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

Servier Bio-Innovation LLC

Start Date

7/9/2024

Completion Date

11/26/2030

Summary

Study CL3-95031-007 (CHONQUER) is a Phase 3, international, multicenter, double-blind, randomized, placebo-controlled study of orally administered ivosidenib. Participants are required to have a histopathological diagnosis consistent with isocitrate dehydrogenase-1 (IDH1) gene-mutated, locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. IDH1 mutant status will be determined during pre-screening/screening phase. Participant must have radiographic progression/recurrence of disease according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and have received 0 to 1 prior systemic treatment regimen in the advanced/metastatic setting for conventional chondrosarcoma. The primary endpoint is progression-free survival (PFS) in Grades 1 and 2 participants. Key secondary endpoints are PFS in all randomized participants, overall survival (OS) in Grades 1 and 2 participants, and OS in all randomized participants. Participants who meet enrollment criteria will be randomized 1:1 to receive oral ivosidenib 500mg once daily, or a matching placebo once daily.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Have a histopathological diagnosis (fresh or banked tumor biopsy sample collected within the last 3 years) consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. * 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. * Have received 0 or 1 prior systemic treatment regimen in the advanced/metastatic setting for chondrosarcoma. * Have radiographic progression/recurrence of disease according to RECIST v1.1 defined as: 1. Radiographic progression of disease (local and/or distant) documented by 2 imaging assessments performed no more than 6 months (±2 weeks) apart within 12 months before randomization. OR 2. Any recurrence of disease (local and/or distant) after complete surgical resection and documented by imaging within 6 months (±2 weeks) before randomization. * Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent 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 tested) * 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: * Are unable to swallow oral medication. * Pregnant or lactating women. * Are participating in another interventional study at the same time; participation in noninterventional registries or epidemiological studies is allowed. * Have received prior therapy with an IDH1 inhibitor * Have received systemic anticancer therapy \<2 weeks prior to randomization (for investigational or immune-based anticancer therapy \<4 weeks). * Have received radiotherapy \<2 weeks prior to randomization. * 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. * 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. * Have had major surgery within 4 weeks prior to randomization. * 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. * Have LVEF \<40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to randomization. * 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). Participants with a bundle branch block combined with a prolonged QTcF interval may be permitted based on local cardiology assessment. * Have known medical history of progressive multifocal leukoencephalopathy (PML).

Interventions

DRUG

Ivosidenib 500mg

DRUG

Placebo

Interested in This Trial?

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Conditions

Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Locations

Usc Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Sarcoma Oncology Research Center

Santa Monica, California 90403

United States

University of Colorado Cancer Center

Aurora, Colorado 80045

United States

Yale Cancer Center

New Haven, Connecticut 06511

United States

Mayo Clinic - Jacksonville, Fl

Jacksonville, Florida 32224

United States

University of Miami

Miami, Florida 33136-1002

United States

Emory Winship Cancer Institute

Atlanta, Georgia 30308

United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois 60611-5975

United States

University of Iowa Hospitals & Clinics- Holden Comprehensive Cancer Center

Iowa City, Iowa 52242

United States

Johns Hopkins University

Baltimore, Maryland 21287

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Mayo Clinic - Rochester, Mn

Rochester, Minnesota 55905

United States

The Washington University

St Louis, Missouri 63110

United States

Nebraska Methodist Hospital

Omaha, Nebraska 68118

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Duke University

Durham, North Carolina 27710

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon 97239

United States

University of Pittsburgh Medical Center-Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

The Univeristy of Texas Md Anderson Cancer Center

Houston, Texas 77030

United States

Flinders Medical Centre

Bedford Park, 5042

Australia

Chris O'Brien Lifehouse

Camperdown, 2050

Australia

Chris O'Brien Lifehouse

Camperdown, 2050

Australia

St Vincent'S Hospital Melbourne

Fitzroy, 3065

Australia

Sir Charles Gairdner Hospital

Nedlands, 6009

Australia

Princess Alexandra Hospital

Woolloongabba, 4102

Australia

Cliniques Universitaires St. Luc

Brussels, 1200

Belgium

U.Z. Gent

Ghent, 9000

Belgium

Centre Multidisciplinaire de Oncologie Medicale

Liège, 4000

Belgium

Liga Norte Riograndense Contra O Cancer

Natal, Rio Grande do Norte 59062-000

Brazil

Hospital de Amor - Barretos

Barretos, 14784-400

Brazil

Hospital Das Clínicas Da Ufmg

Belo Horizonte, 30130-100

Brazil

CIONC

Curitiba, 80810-050

Brazil

Cepon - Centro de Pesquisas Oncologicas

Florianópolis, 88034-000

Brazil

Fundação Amaral Carvalho - Jaú/ Sp

Jaú, 17210-080

Brazil

Instituto Nacional Do Câncer - Inca

Rio de Janeiro, 20220-410

Brazil

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, 01246-000

Brazil

Impar Serviços Hospitalares S.A. - Hospital Nove de Julho

São Paulo, 01409-902

Brazil

Hospital A C Camargo

São Paulo, 01509-010

Brazil

Hospital Albert Einstein

São Paulo, 05652-900

Brazil

Alberta Health Services

Calgary, Alberta T2N-5G2

Canada

University Health Network

Toronto, Ontario M5G 2M9

Canada

Muhc Glen Site

Montreal, Quebec H4A 3J1

Canada

The First Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong 510080

China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei 430023

China

Shanghai Changzheng Hospital

Shang'ai, Shanghai Municipality 200000

China

Shanghai Ruijin Hospital

Shanghai, Shanghai Municipality 200025

China

Shanghai General Hospital

Shanghai, Shanghai Municipality 200080

China

West China Hopital of Sichuan University

Chengdu, Sichuan 610041

China

The Second Affiliated Hospital Zhejiang University School of Medical

Hangzhou, Zhejiang 310025

China

Beijing Cancer Hospital

Beijing, 100142

China

Beijing Jishuitan Hospital

Beijing, 102208

China

Henan Cancer Hospital

Guangzhou, 450003

China

Aarhus Universitetshospital

Aarhus, 8200

Denmark

Herlev & Gentofte Hospital

Herlev, 2730

Denmark

Institut Bergonié

Bordeaux, 33076

France

Centre Oscar Lambret

Lille, 59020

France

Hôpital Léon Bérard

Lyon, 69008

France

Hopital de La Timone

Marseille, 13005

France

Hôpital Cochin

Paris, 75014

France

INSTITUT de CANCEROLOGIE de l'Ouest

Saint-Herblain, 44805

France

Iuct-Oncopole Institut Universitaire Du Cancer

Toulouse, 31059

France

Institut Gustave Roussy

Villejuif, 94800

France

Helios Klinikum Bad Saarow

Bad Saarow, 15526

Germany

Charite Universitatsmedizin

Berlin, 13353

Germany

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307

Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20246

Germany

Universitätsmedizin Mannheim (Umm)

Mannheim, 68167

Germany

Lmu Klinikum

München, 81377

Germany

Ukm - Sarkom-Zentrum

Münster, 48149

Germany

Universitaetsklinikum Ulm

Ulm, 89081

Germany

Irccs Istituto Ortopedico Rizzoli

Bologna, 40136

Italy

Irccs Fondazione Istituto Nazionale Dei Tumori

Milan, 20133

Italy

San Luigi Gonzaga University Hospital of Turin

Orbassano, 10043

Italy

Istituto Oncologico Veneto Iov - Irccs

Padova, 35128

Italy

Aou Policlinico Paolo Giaccone

Palermo, 90127

Italy

Ospedale Santo Stefano

Prato, 59100

Italy

Policlinico Universitario Campus Biomedico

Roma, 00128

Italy

Istituti Fisioterapici Ospitalieri (Ifo) - Istituto Nazionale Tumori Regina Elena (Ire)

Roma, 00144

Italy

Hokkaido Cancer Center

Sapporo, Hokkaido 003-0804

Japan

Kanazawa University Hospital

Kanazawa, Ishikawa-ken 920-8641

Japan

Nagoya University Hospital

Shōwaku, Nagoya-shi, Aichi 466-8560

Japan

Niigata University Medical and Dental General Hospital

Chūōku, Niigata City 951-8510

Japan

Oita University Hospital

Yufu-Shi, Oita Prefecture 879-5593

Japan

Osaka International Cancer Institute

Chūōku, Osaka-shi, Osaka 700-8558

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045

Japan

Fukushima Medical University Hospital

Fukushima, 960-1295

Japan

Kyushu University Hospital

Higashi, 812-8582

Japan

Cancer Institute Hospital of Jfcr

Koto-Ku, Tokyo, 135-8550

Japan

Okayama University Hospital

Okayama, 700-8558

Japan

Universitair Medisch Centrum Groningen (Umcg)

Groningen, 9713 GZ

Netherlands

Leids Universitair Medisch Centrum

Leiden, 2333 ZA

Netherlands

Radboud Umc

Nijmegen, 6525 GA

Netherlands

Pan American Center For Oncology Trials, LLC

Rio Piedras, 00935

Puerto Rico

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitario Valle de Hebrón - Vhio

Barcelona, 08035

Spain

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041

Spain

Hospital de Bellvitge - Ico

L'Hospitalet de Llobregat, 08908

Spain

Hospital General Universitario Gregorio

Madrid, 28007

Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Universitario Y Politecnico La Fe

Valencia, 46026

Spain

National Taiwan University Hospital

Taipei, 100225

Taiwan

Taipei Veterans General Hospital

Taipei, 112201

Taiwan

Western General Hospital

Edinburgh,

United Kingdom

Royal Marsden Hospital

London,

United Kingdom

UCLH

London,

United Kingdom

Christie Hospital

Manchester, M20 4BX

United Kingdom

Churchill Hospital

Oxford,

United Kingdom