Clinical trial NCT06127407: Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen
Keywords: Conventional chondrosarcoma
IDH1
ivosidenib
locally advanced
metastatic
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherches Internationales Servier
First posted: 2023-11-13
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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).

Primary outcomes:
measure: Progression-free survival (PFS) based on Blinded Independent Central Reviewer (BICR) assessment in Grade 1 and Grade 2 participants
timeFrame: Up to approximately 31 months
Secondary outcomes:
measure: PFS based on BICR assessment in all randomized participants
timeFrame: Up to approximately 31 months
measure: Overall survival (OS) in Grade 1 and Grade 2 participants
timeFrame: Up to 5 years
measure: OS in all randomized participants
timeFrame: Up to 5 years
measure: PFS based on Investigator assessment in Grade 1 and Grade 2 participants
timeFrame: Up to approximately 31 months
measure: PFS based on Investigator assessment in all randomized participants
timeFrame: Up to approximately 31 months
measure: 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
timeFrame: Up to approximately 31 months
measure: OR (confirmed CR or confirmed PR) of anti-tumor activity (using RECIST v1.1) in all randomized participants
timeFrame: Up to approximately 31 months
measure: Duration of response (DOR) in Grade 1 and Grade 2 participants
timeFrame: Up to approximately 31 months
measure: DOR in all randomized participants
timeFrame: Up to approximately 31 months
measure: Time to response (TTR) in Grade 1 and Grade 2 participants
timeFrame: Up to approximately 31 months
measure: TTR in all randomized participants
timeFrame: Up to approximately 31 months
measure: Disease control (DC) confirmed CR, confirmed PR, or stable disease (SD)) in Grade 1 and Grade 2 participants
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
measure: DC (confirmed CR, confirmed PR, or SD) in all randomized participants
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
measure: Duration of disease control (DoDC) in Grade 1 and Grade 2 participants
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
measure: DoDC in all randomized participants
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
measure: Number of Adverse Events (AEs)
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Number of Serious Adverse Events (SAEs)
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Number of Adverse Events of Special Interest (AESIs)
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Number of Adverse Events (AEs) leading to discontinuation, treatment interruption, and dose reduction
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) score
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) score
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) score
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Ivosidenib concentration in plasma
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
measure: 2-hydroxyglutarate (2-HG) concentration in plasma
timeFrame: Through the end of the study (a maximum of 5 years after the study start)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville, Fl
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics- Holden Comprehensive Cancer Center
state: Iowa
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester, Mn
state: Minnesota
city: Saint Louis
country: United States
facility: The Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Knight Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center-Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The Univeristy of Texas Md Anderson Cancer Center
state: Texas
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Fitzroy
country: Australia
facility: St Vincent'S Hospital Melbourne
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Barretos
country: Brazil
facility: Hospital de Amor - Barretos
city: Belo Horizonte
country: Brazil
facility: Hospital Das Clínicas Da Ufmg
city: Curitiba
country: Brazil
facility: CIONC
city: Florianópolis
country: Brazil
facility: Cepon - Centro de Pesquisas Oncologicas
city: Jaú
country: Brazil
facility: Fundação Amaral Carvalho - Jaú/ Sp
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional Do Câncer - Inca
city: São Paulo
country: Brazil
facility: Icesp - Instituto Do Câncer Do Estado de São Paulo
city: São Paulo
country: Brazil
facility: Impar Serviços Hospitalares S.A. - Hospital Nove de Julho
city: São Paulo
country: Brazil
facility: Hospital A C Camargo
city: São Paulo
country: Brazil
facility: Hospital Albert Einstein
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Muhc Glen Site
state: Quebec
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medical
state: Zhejiang
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
city: Palermo
country: Italy
facility: Aou Policlinico Paolo Giaccone
city: Prato
country: Italy
facility: Ospedale Santo Stefano
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri (Ifo) - Istituto Nazionale Tumori Regina Elena (Ire)
city: Sapporo
country: Japan
facility: Hokkaido Cancer Center
state: Hokkaido
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Showa-ku
country: Japan
facility: Nagoya University Hospital
state: Nagoya-shi, Aichi
city: Yufu-Shi
country: Japan
facility: Oita University Hospital
state: Oita
city: Chuo Ku
country: Japan
facility: Osaka International Cancer Institute
state: Osaka-shi, Osaka
city: Chuo-ku, Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Higashi
country: Japan
facility: Kyushu University Hospital
city: Koto-Ku, Tokyo
country: Japan
facility: Cancer Institute Hospital of Jfcr
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen (Umcg)
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud Umc
city: Barcelona
country: Spain
facility: Hospital Universitario Valle de Hebrón - Vhio
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital de Bellvitge - Ico
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitario Y Politecnico La Fe
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: UCLH
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
References: