Ivosidenib in participants with locally advanced or metastatic conventional chondrosarcoma untreated or previously treated with 1 systemic treatment regimen.
- Conditions
- Locally advanced or metastatic conventional chondrosarcoma with an IDH1 mutation, untreated or previously treated with 1 systemic treatment regimen
- Registration Number
- 2023-508507-20-00
- Brief Summary
To assess the efficacy of ivosidenib treatment based on tumor assessments by a Blinded Independent Central Reviewer (BICR) in Grade 1 and Grade 2 participants
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Not specified
- Target Recruitment
- 57
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 or other local therapeutic options as per standard of care such as definitive radiotherapy for skull base lesions.
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.Only for participants with conventional chondrosarcoma Grade 3, a maximum of 2 prior systemic treatment regimens in advanced/metastatic setting are allowed.
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.
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)
Have recovered from any clinically relevant sequelae and toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
Are unable to swallow oral medication.
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, 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.
Have known medical history of progressive multifocal leukoencephalopathy (PML).
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants
- Secondary Outcome Measures
Name Time Method PFS based on BICR assessment in all randomized participants PFS based on BICR assessment in all randomized participants
Overall survival (OS) in Grade 1 and Grade 2 participants Overall survival (OS) in Grade 1 and Grade 2 participants
OS in all randomized participants OS in all randomized participants
PFS based on Investigator assessment in Grade 1 and Grade 2 participants and in all randomised participants PFS based on Investigator assessment in Grade 1 and Grade 2 participants and in all randomised participants
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 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
Duration of response (DOR) in Grade 1 and Grade 2 participants and in all randomised participants Duration of response (DOR) in Grade 1 and Grade 2 participants and in all randomised participants
Time to response (TTR) in Grade 1 and Grade 2 participants and in all randomised participants Time to response (TTR) in Grade 1 and Grade 2 participants and in all randomised participants
Disease control (DC) CR, PR, or stable disease (SD)) in Grade 1 and Grade 2 participants and in all randomised participants Disease control (DC) CR, PR, or stable disease (SD)) in Grade 1 and Grade 2 participants and in all randomised participants
Duration of disease control (DoDC) in Grade 1 and Grade 2 participants and in all randomised participants Duration of disease control (DoDC) in Grade 1 and Grade 2 participants and in all randomised participants
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 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
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score
European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score
Patient-Reported Outcomes Measurement Information System (PROMIS) score Patient-Reported Outcomes Measurement Information System (PROMIS) score
Ivosidenib and 2-hydroxyglutarate (2-HG) concentration in plasma Ivosidenib and 2-hydroxyglutarate (2-HG) concentration in plasma
Trial Locations
- Locations (75)
Usc Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Mayo Clinic - Jacksonville, Fl
🇺🇸Jacksonville, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals & Clinics- Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Scroll for more (65 remaining)Usc Norris Comprehensive Cancer Center🇺🇸Los Angeles, California, United States