Ivosidenib for advanced or metastatic chondrosarcoma with IDH1 mutation

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 3, international, multicenter, double-blind, randomized, placebo-controlled study evaluates the efficacy of orally administered ivosidenib in participants with locally advanced or metastatic conventional chondrosarcoma that has an IDH1 mutation. Eligible participants must have a histopathological diagnosis and have received 0 to 1 prior systemic treatment regimen. The primary endpoint is progression-free survival in Grades 1 and 2 participants, with secondary endpoints including overall survival. The study aims to determine the effectiveness of ivosidenib in improving patient outcomes compared to placebo.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Have a histopathological diagnosis 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 to 2 prior systemic treatment regimens 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).

Where it's running

• Sarcoma Oncology Research Center
  Santa Monica, California, United States Recruiting
• University of Colorado Cancer Center
  Aurora, Colorado, United States Recruiting
• Yale Cancer Center
  New Haven, Connecticut, United States Recruiting
• Mayo Clinic - Jacksonville, Fl
  Jacksonville, Florida, United States Recruiting
• University of Miami
  Miami, Florida, United States Recruiting
• Emory Winship Cancer Institute
  Atlanta, Georgia, United States Recruiting

+65 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
• Email: scientificinformation@servier.com
• Phone: +33 1 55 72 60 00

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.