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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06127407




Registration number
NCT06127407
Ethics application status
Date submitted
7/11/2023
Date registered
13/11/2023

Titles & IDs
Public title
Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen
Scientific title
A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Study of Ivosidenib in Participants =18 Years of Age With Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen
Secondary ID [1] 0 0
CL3-95031-007
Universal Trial Number (UTN)
Trial acronym
CHONQUER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ivosidenib 500mg
Treatment: Drugs - Placebo

Experimental: Ivosidenib - Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years).

Placebo comparator: Placebo - Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years). Participants randomized to the placebo arm who experience BICR-confirmed disease progression and meet the crossover eligibility criteria will be given the opportunity to cross over and receive ivosidenib.


Treatment: Drugs: Ivosidenib 500mg
Provided as tablets, taken orally as two 250mg tablets once daily.

Treatment: Drugs: Placebo
Provided as tablets, taken orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants
Timepoint [1] 0 0
Up to approximately 31 months
Secondary outcome [1] 0 0
PFS based on BICR assessment in all randomized participants
Timepoint [1] 0 0
Up to approximately 31 months
Secondary outcome [2] 0 0
Overall survival (OS) in Grade 1 and Grade 2 participants
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
OS in all randomized participants
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
PFS based on Investigator assessment in Grade 1 and Grade 2 participants
Timepoint [4] 0 0
Up to approximately 31 months
Secondary outcome [5] 0 0
PFS based on Investigator assessment in all randomized participants
Timepoint [5] 0 0
Up to approximately 31 months
Secondary outcome [6] 0 0
Objective response (OR) (confirmed complete response(CR) or confirmed partial response (PR)) of anti-tumor activity (using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) in Grade 1 and Grade 2 participants
Timepoint [6] 0 0
Up to approximately 31 months
Secondary outcome [7] 0 0
OR (confirmed CR or confirmed PR) of anti-tumor activity (using RECIST v1.1) in all randomized participants
Timepoint [7] 0 0
Up to approximately 31 months
Secondary outcome [8] 0 0
Duration of response (DOR) in Grade 1 and Grade 2 participants
Timepoint [8] 0 0
Up to approximately 31 months
Secondary outcome [9] 0 0
DOR in all randomized participants
Timepoint [9] 0 0
Up to approximately 31 months
Secondary outcome [10] 0 0
Time to response (TTR) in Grade 1 and Grade 2 participants
Timepoint [10] 0 0
Up to approximately 31 months
Secondary outcome [11] 0 0
TTR in all randomized participants
Timepoint [11] 0 0
Up to approximately 31 months
Secondary outcome [12] 0 0
Disease control (DC) confirmed CR, confirmed PR, or stable disease (SD)) in Grade 1 and Grade 2 participants
Timepoint [12] 0 0
Through the end of the study (a maximum of 5 years after the study start)
Secondary outcome [13] 0 0
DC (confirmed CR, confirmed PR, or SD) in all randomized participants
Timepoint [13] 0 0
Through the end of the study (a maximum of 5 years after the study start)
Secondary outcome [14] 0 0
Duration of disease control (DoDC) in Grade 1 and Grade 2 participants
Timepoint [14] 0 0
Through the end of the study (a maximum of 5 years after the study start)
Secondary outcome [15] 0 0
DoDC in all randomized participants
Timepoint [15] 0 0
Through the end of the study (a maximum of 5 years after the study start)
Secondary outcome [16] 0 0
Number of Adverse Events (AEs)
Timepoint [16] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [17] 0 0
Number of Serious Adverse Events (SAEs)
Timepoint [17] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [18] 0 0
Number of Adverse Events of Special Interest (AESIs)
Timepoint [18] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [19] 0 0
Number of Adverse Events (AEs) leading to discontinuation, treatment interruption, and dose reduction
Timepoint [19] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [20] 0 0
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score
Timepoint [20] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [21] 0 0
European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score
Timepoint [21] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [22] 0 0
Patient-Reported Outcomes Measurement Information System (PROMIS) score
Timepoint [22] 0 0
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Secondary outcome [23] 0 0
Ivosidenib concentration in plasma
Timepoint [23] 0 0
Through the end of the study (a maximum of 5 years after the study start)
Secondary outcome [24] 0 0
2-hydroxyglutarate (2-HG) concentration in plasma
Timepoint [24] 0 0
Through the end of the study (a maximum of 5 years after the study start)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/11/2030
Actual
Sample size
Target
136
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Brazil
State/province [14] 0 0
Barretos
Country [15] 0 0
Brazil
State/province [15] 0 0
Belo Horizonte
Country [16] 0 0
Brazil
State/province [16] 0 0
Curitiba
Country [17] 0 0
Brazil
State/province [17] 0 0
Florianópolis
Country [18] 0 0
Brazil
State/province [18] 0 0
Jaú
Country [19] 0 0
Brazil
State/province [19] 0 0
Rio De Janeiro
Country [20] 0 0
Brazil
State/province [20] 0 0
São Paulo
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Japan
State/province [23] 0 0
Hokkaido
Country [24] 0 0
Japan
State/province [24] 0 0
Ishikawa
Country [25] 0 0
Japan
State/province [25] 0 0
Nagoya-shi, Aichi
Country [26] 0 0
Japan
State/province [26] 0 0
Osaka-shi, Osaka
Country [27] 0 0
Japan
State/province [27] 0 0
Chuo-ku, Tokyo
Country [28] 0 0
Japan
State/province [28] 0 0
Higashi
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Japan
State/province [30] 0 0
Yufu-shi, Oita
Country [31] 0 0
Japan
State/province [31] 0 0
Yufu

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Servier Bio-Innovation LLC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Institut de Recherches Internationales Servier
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
Address 0 0
Country 0 0
Phone 0 0
+33 1 55 72 60 00
Fax 0 0
Email 0 0
scientificinformation@servier.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorization in EEA or US if the study is used for the approval.
Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicaltrials.servier.com/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06127407