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

Last updated: March 11, 2025
Sponsor: Servier Bio-Innovation LLC
Overall Status: Active - Recruiting

Phase

3

Condition

Sarcoma (Pediatric)

Bone Neoplasm

Sarcoma

Treatment

Ivosidenib 500mg

Placebo

Clinical Study ID

NCT06127407
CL3-95031-007
  • Ages > 18
  • All Genders

Study 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

Inclusion

Inclusion Criteria:

  • Have a histopathological diagnosis (fresh or banked tumor biopsy sample collectedwithin the last 3 years) consistent with locally advanced or metastatic conventionalchondrosarcoma 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 providedmeasurable disease falls outside of the treatment field or within the field and hasshown ≥20% growth in size since post-treatment assessment.

  • Have received 0 or 1 prior systemic treatment regimen in the advanced/metastaticsetting for chondrosarcoma.

  • Have radiographic progression/recurrence of disease according to RECIST v1.1 definedas:

  1. Radiographic progression of disease (local and/or distant) documented by 2imaging assessments performed no more than 6 months (±2 weeks) apart within 12months before randomization.OR

  2. Any recurrence of disease (local and/or distant) after complete surgicalresection and documented by imaging within 6 months (±2 weeks) beforerandomization.

  • Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the mostrecent banked tumor tissue available that was sourced from either a primary ormetastatic tumor lesion) based on central laboratory testing (R132C/L/G/H/S mutationvariants tested)

  • Have recovered from any clinically relevant sequelae and toxic effects of any priorsurgery, radiotherapy, or other therapy intended for the treatment of cancer.

Exclusion

Exclusion Criteria:

  • Are unable to swallow oral medication.

  • Pregnant or lactating women.

  • Are participating in another interventional study at the same time; participation innoninterventional registries or epidemiological studies is allowed.

  • Have received prior therapy with an IDH1 inhibitor

  • Have received systemic anticancer therapy <2 weeks prior to randomization (forinvestigational 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 areeligible if they have completed their treatment and have recovered from the acuteeffects of radiation therapy or surgery prior to randomization, have discontinued orreduced corticosteroid treatment <=10 mg per day for these metastases for at least 4weeks and have radiographically stable disease of brain lesions for at least 3months prior to randomization.

  • Have a history of another primary cancer, with the exception of: a) curativelyresected 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 primarysolid or liquid tumor for ≥ 1 year prior to the start of study treatment and, in theopinion of the Investigator, the disease will not affect participant's outcome inthe 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 heartfailure; myocardial infarction; unstable angina; and/or stroke.

  • Have LVEF <40% by ECHO scan (or by other methods according to institutionalpractice) obtained within 28 days prior to randomization.

  • Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450msec 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 maybe permitted based on local cardiology assessment.

  • Have known medical history of progressive multifocal leukoencephalopathy (PML).

Study Design

Total Participants: 136
Treatment Group(s): 2
Primary Treatment: Ivosidenib 500mg
Phase: 3
Study Start date:
July 09, 2024
Estimated Completion Date:
November 26, 2030

Connect with a study center

  • Flinders Medical Centre

    Bedford Park, 5042
    Australia

    Active - Recruiting

  • Chris O'Brien Lifehouse

    Camperdown, 2050
    Australia

    Site Not Available

  • St Vincent'S Hospital Melbourne

    Fitzroy, 3065
    Australia

    Active - Recruiting

  • Sir Charles Gairdner Hospital

    Nedlands, 6009
    Australia

    Active - Recruiting

  • Princess Alexandra Hospital

    Woolloongabba, 4102
    Australia

    Active - Recruiting

  • Hospital de Amor - Barretos

    Barretos, 14784-400
    Brazil

    Active - Recruiting

  • Hospital Das Clínicas Da Ufmg

    Belo Horizonte, 30130-100
    Brazil

    Active - Recruiting

  • CIONC

    Curitiba, 80810-050
    Brazil

    Active - Recruiting

  • Cepon - Centro de Pesquisas Oncologicas

    Florianópolis, 88034-000
    Brazil

    Active - Recruiting

  • Fundação Amaral Carvalho - Jaú/ Sp

    Jaú, 17210-080
    Brazil

    Active - Recruiting

  • Instituto Nacional Do Câncer - Inca

    Rio De Janeiro, 20220-410
    Brazil

    Active - Recruiting

  • Hospital A C Camargo

    São Paulo, 01509-010
    Brazil

    Active - Recruiting

  • Hospital Albert Einstein

    São Paulo, 05652-900
    Brazil

    Active - Recruiting

  • Icesp - Instituto Do Câncer Do Estado de São Paulo

    São Paulo, 01246-000
    Brazil

    Active - Recruiting

  • UNIVERSITY HEALTH NETWORK, Princess Margaret Cancer Centre,

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • University Health Network

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • Muhc Glen Site

    Montréal, Quebec H4A 3J1
    Canada

    Active - Recruiting

  • Hokkaido Cancer Center

    Sapporo, Hokkaido 003-0804
    Japan

    Active - Recruiting

  • Kanazawa University Hospital

    Kanazawa, Ishikawa 920-8641
    Japan

    Active - Recruiting

  • Nagoya University Hospital

    Showa-ku, Nagoya-shi, Aichi 466-8560
    Japan

    Active - Recruiting

  • Oita University Hospital

    Yufu, Oita 879-5503
    Japan

    Active - Recruiting

  • Osaka International Cancer Institute

    Chuo Ku, Osaka-shi, Osaka 700-8558
    Japan

    Active - Recruiting

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045
    Japan

    Active - Recruiting

  • Kyushu University Hospital

    Higashi, 812-8582
    Japan

    Active - Recruiting

  • Cancer Institute Hospital of Jfcr

    Koto-Ku, Tokyo, 135-8550
    Japan

    Active - Recruiting

  • Cancer Institute Hospital of Jfcr

    Tokyo, 135-8550
    Japan

    Site Not Available

  • Okayama University Hospital

    Yufu, 879-5503
    Japan

    Active - Recruiting

  • Okayama University Hospital

    Yufu-shi, 879-5503
    Japan

    Active - Recruiting

  • Oita University Hospital

    Yufu-shi, Oita, 879-5503
    Japan

    Site Not Available

  • Royal Marsden Hospital

    London,
    United Kingdom

    Active - Recruiting

  • Christie Hospital

    Manchester, M20 4BX
    United Kingdom

    Active - Recruiting

  • Usc Norris Comprehensive Cancer Center

    Los Angeles, California 90033
    United States

    Active - Recruiting

  • Sarcoma Oncology Research Center

    Santa Monica, California 90403
    United States

    Active - Recruiting

  • University of Colorado Cancer Center

    Aurora, Colorado 80045
    United States

    Active - Recruiting

  • Yale Cancer Center

    New Haven, Connecticut 06511
    United States

    Active - Recruiting

  • Mayo Clinic - Jacksonville, Fl

    Jacksonville, Florida 32224
    United States

    Active - Recruiting

  • University of Miami

    Miami, Florida 33136-1002
    United States

    Active - Recruiting

  • Emory Winship Cancer Institute

    Atlanta, Georgia 30308
    United States

    Site Not Available

  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University

    Chicago, Illinois 60611-5975
    United States

    Active - Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Mayo Clinic - Rochester, Mn

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • The Washington University

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Nebraska Methodist Hospital

    Omaha, Nebraska 68118
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Active - Recruiting

  • Duke University

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • Usc Norris Comprehensive Cancer Center

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • Cleveland Clinic

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • Oregon Health & Science University Knight Cancer Institute

    Portland, Oregon 97239
    United States

    Active - Recruiting

  • The Univeristy of Texas Md Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

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