Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
ClarIDHy
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
1 other identifier
interventional
187
6 countries
49
Brief Summary
Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of orally administered AG-120. Participants, all personnel involved in the evaluation of participants' response to treatment (e.g., Investigators, study coordinators, study pharmacists), and designated Sponsor team members will be blinded to study treatment. Participants are required to have a histologically-confirmed diagnosis of isocitrate dehydrogenase-1 (IDH1) gene-mutated cholangiocarcinoma that is not eligible for curative resection, transplantation, or ablative therapies prior to enrollment. IDH1 mutation testing will be performed at participating investigative sites. Participants must have progression of disease and have received at least 1 but not more than 2 prior treatment regimens for advanced disease (nonresectable or metastatic). All participants must have received either a gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2017
Typical duration for phase_3
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 5, 2016
CompletedFirst Posted
Study publicly available on registry
December 12, 2016
CompletedStudy Start
First participant enrolled
February 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
May 17, 2021
CompletedResults Posted
Study results publicly available
April 13, 2022
CompletedAugust 20, 2024
July 1, 2024
1.9 years
December 5, 2016
January 28, 2022
July 24, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)
PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.
From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)
Secondary Outcomes (31)
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)
Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events
From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)
Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs
From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Baseline
Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment
From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)
- +26 more secondary outcomes
Study Arms (3)
AG-120
ACTIVE COMPARATORParticipants received AG-120 500 mg, tablet, orally, once a day (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.
Placebo
PLACEBO COMPARATORParticipants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.
After Cross over to AG-120
EXPERIMENTALParticipants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.
Interventions
Eligibility Criteria
You may qualify if:
- Be ≥18 years of age.
- Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies.
- Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on central laboratory testing (R132C/L/G/H/S mutation variants tested).
- Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
- Have an expected survival of ≥3 months.
- Have at least one evaluable and measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or 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 documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic). Participants must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced cholangiocarcinoma. Participants who have received systemic adjuvant chemotherapy will be permitted provided there is documented disease progression during or within 6 months of completing the therapy.
You may not qualify if:
- Received a prior IDH inhibitor.
- Received systemic anticancer therapy or an investigational agent \<2 weeks prior to Day 1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the first dose of study treatment should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
- Received radiotherapy to metastatic sites of disease \<2 weeks prior to Day 1.
- Underwent hepatic radiation, chemoembolization, and radiofrequency ablation \<4 weeks prior to Day 1.
- Have known symptomatic brain metastases requiring steroids. 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 study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and have radiographically stable disease for at least 3 months prior to study entry. Note: up to 10 mg per day of prednisone equivalent will be allowed.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (49)
Mayo Cancer Center
Scottsdale, Arizona, 85054, United States
City of Hope Cancer Center
Duarte, California, 91010, United States
University of California, Irvine
Irvine, California, 92868, United States
University of Southern California
Los Angeles, California, 90033, United States
University of California, San Francisco
San Francisco, California, 94158, United States
Mayo Cancer Center
Jacksonville, Florida, 32224, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Cancer Center
Rochester, Minnesota, 55905, United States
Washington University
St Louis, Missouri, 63110, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021, United States
Columbia University
New York, New York, 10032, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Gibbs Cancer Center
Spartanburg, South Carolina, 29303, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Texas, SouthWestern
Dallas, Texas, 75390, United States
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
University of Wisconsin, Carbone Cancer Center
Madison, Wisconsin, 53792, United States
Universite de Franche-Comte
Besançon, 25000, France
Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie
Bordeaux, 33076, France
Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer
Rennes, 35042, France
Institut Gustave Roussy
Villejuif, 94805, France
Fondazione del Piemonte per l'Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS Candiolo)
Candiolo, 10060, Italy
Istituto Scientifico Universitario San Raffaele
Milan, 20127, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
Seoul National University Hospital
Seoul, 03080, South Korea
Yonsei University Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Seoul, St. Mary's Hospital
Seoul, 06591, South Korea
National Cancer Center
Seoul, 10408, South Korea
Hospital Vall d'Hebrón
Barcelona, 08035, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Hospital Universitario Marques de Valdecilla
Santander, 39008, Spain
St. James University Hospital
Leeds, LS16 6QB, United Kingdom
Liverpool Cancer Center
Liverpool, CH63 4JY, United Kingdom
University College London Hospitals
London, NW1 2PG, United Kingdom
The Royal Free Hospital
London, NW3 2QG, United Kingdom
The Christie NHS Foundation Trust, the Christie Hospital
Manchester, M20 4QL, United Kingdom
Related Publications (3)
Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13.
PMID: 32416072BACKGROUNDFan B, Abou-Alfa GK, Zhu AX, Pandya SS, Jia H, Yin F, Gliser C, Hua Z, Hossain M, Yang H. Pharmacokinetics/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study. Cancer Chemother Pharmacol. 2024 May;93(5):471-479. doi: 10.1007/s00280-023-04633-5. Epub 2024 Jan 27.
PMID: 38278871DERIVEDZhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DVT, Borad MJ, Bridgewater JA, Harris WP, Murphy AG, Oh DY, Whisenant JR, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Chamberlain CX, Aguado-Fraile E, Choe S, Wu B, Liu H, Gliser C, Pandya SS, Valle JW, Abou-Alfa GK. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021 Nov 1;7(11):1669-1677. doi: 10.1001/jamaoncol.2021.3836.
PMID: 34554208DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Affairs
- Organization
- Servier Pharmaceuticals LLC
Study Officials
- STUDY CHAIR
Medical Affairs Servier Pharmaceuticals LLC
Servier Pharmaceuticals, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2016
First Posted
December 12, 2016
Study Start
February 20, 2017
Primary Completion
January 31, 2019
Study Completion
May 17, 2021
Last Updated
August 20, 2024
Results First Posted
April 13, 2022
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- After Marketing Authorisation in EEA or US if the study is used for the approval.
- Access Criteria
- 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.
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.