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Advanced CholangiocarcinomaPhase 3ClarIDHyNCT02989857

Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)

A Phase 3 study testing AG-120 in people with Advanced Cholangiocarcinoma and Metastatic Cholangiocarcinoma, run by Institut de Recherches Internationales Servier at 49 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AG-120
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
187 participants
Where
49 sitesin 6 countries
Study dates
20 Feb 2017to 17 May 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

49 sites in 6 countries.

49 sites in 6 countries

United States26 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • University of Texas, SouthWestern

    Dallas, Texas, 75390

  • City of Hope Cancer Center

    Duarte, California, 91010

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California, Irvine

    Irvine, California, 92868

  • Mayo Cancer Center

    Jacksonville, Florida, 32224

  • University of Southern California

    Los Angeles, California, 90033

  • University of Wisconsin, Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • Columbia University

    New York, New York, 10032

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Cancer Center

    Rochester, Minnesota, 55905

  • University of Utah, Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • University of California, San Francisco

    San Francisco, California, 94158

  • Mayo Cancer Center

    Scottsdale, Arizona, 85054

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Gibbs Cancer Center

    Spartanburg, South Carolina, 29303

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

South Korea6 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Yonsei University Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • Seoul, St. Mary's Hospital

    Seoul, 06591

  • National Cancer Center

    Seoul, 10408

Other trials in South Korea

Spain5 sites

  • Hospital Vall d'Hebrón

    Barcelona, 08035

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Centro Integral Oncologico Clara Campal

    Madrid, 28050

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

Other trials in Spain

United Kingdom5 sites

  • St. James University Hospital

    Leeds, LS16 6QB

  • Liverpool Cancer Center

    Liverpool, CH63 4JY

  • University College London Hospitals

    London, NW1 2PG

  • The Royal Free Hospital

    London, NW3 2QG

  • The Christie NHS Foundation Trust, the Christie Hospital

    Manchester, M20 4QL

Other trials in United Kingdom

France4 sites

  • Universite de Franche-Comte

    Besançon, 25000

  • Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie

    Bordeaux, 33076

  • Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

    Rennes, 35042

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Italy3 sites

  • Fondazione del Piemonte per l'Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS Candiolo)

    Candiolo, 10060

  • Istituto Scientifico Universitario San Raffaele

    Milan, 20127

  • Istituto Clinico Humanitas

    Rozzano, 20089

Other trials in Italy

About this study

Official title: 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

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.

Being tested
AG-120, Placebo
Keywords
IDH1
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AG-120Drug

    Also called Ivosidenib

    Tablet administered orally

  • PlaceboDrug

    Tablet administered orally

Study groups in NCT02989857
Study groupRoleWhat they receive
AG-120Active 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.
Receives: Drug: AG-120
PlaceboPlacebo 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.
Receives: Drug: Placebo
After Cross over to AG-120ExperimentalParticipants 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.
Receives: Drug: AG-120

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported.

    Measured: From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)

  2. Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events

    The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.

    Measured: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)

  3. Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs

    Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03.

    Measured: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)

  4. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

    The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status.

    Measured: Baseline

  5. Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment

    Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported.

    Measured: From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)

  6. Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events

    Measured: Pre-dose C1D1, C2D1; Post-dose C1D1, C1D15, C2D1 and Day 1 of C3D1 and all cycles thereafter up to last dose plus 28 days (Up to approximately 4 years)

  7. Overall Survival (OS)

    Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier.

    Measured: From date of randomization until the date of death due to any cause (Up to approximately 2 years)

  8. Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1

    ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.

    Measured: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)

  9. ORR as Assessed by the IRC Per RECIST v1.1

    ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.

    Measured: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)

  10. Duration of Response (DOR) as Assessed by the Investigator

    DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.

    Measured: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)

  11. DOR as Assessed by the IRC Per RECIST v1.1

    DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.

    Measured: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)

  12. Time to Response (TTR) as Assessed by the Investigator

    TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.

    Measured: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)

  13. TTR as Assessed by the IRC Per RECIST v1.1

    TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.

    Measured: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)

  14. PFS as Determined by Investigator

    PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% 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 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date.

    Measured: 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)

  15. Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores

    EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100.

    Measured: Cycle 2 Day 1 and Cycle 3 Day 1

  16. Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)

    For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement).

    Measured: Cycle 2 Day 1 and Cycle 3 Day 1

  17. Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)

    The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal.

    Measured: Cycle 2 Day 1 and Cycle 3 Day 1

  18. Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)

    The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal.

    Measured: Cycle 2 Day 1 and Cycle 3 Day 1

  19. Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response

    The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal.

    Measured: Cycle 3 Day 1

  20. Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score

    The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine." Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome).

    Measured: Cycle 3 Day 1

  21. Maximum Observed Plasma Concentration (Cmax) of AG-120

    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  22. Time to Reach Maximal Plasma Concentration (Tmax) of AG-120

    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  23. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)

    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

    Measured: Post-dose of Cycle 2 Day 1 (each cycle = 28 days)

  24. Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)

    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  25. Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)

    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

    Measured: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

  26. Accumulation Ratio Based on Cmax (Racc Cmax)

    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

    Measured: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

  27. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)

    B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  28. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4

    AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  29. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4

    %BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.

    Measured: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

  30. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough

    Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

    Measured: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

  31. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough

    %BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

    Measured: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2016 (estimated)
  2. Study start20 Feb 2017
  3. Primary completion31 Jan 2019
  4. Study completion17 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients randomized in a 2:1 allocation (AG-120 vs Placebo)
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
187 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02989857
Sponsor's protocol ID
AG120-C-005
Acronym
ClarIDHy
Status last verified
Jul 2024
First submitted
5 Dec 2016
Last updated
20 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 32416072

  • Valle JW, Abou-Alfa GK, Kelley RK, Lowery MA, Shroff RT, Bian Y, Saint-Hilary G, Liu H, Teng Z, Hua Z, Gliser C, Vogel A, Javle MM. Quantitative benefit-risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma. ESMO Gastrointest Oncol. 2025 Apr 3;8:100159. doi: 10.1016/j.esmogo.2025.100159. eCollection 2025 Jun.

    PubMed 41646284

  • Fan 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.

    PubMed 38278871

  • Zhu 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.

    PubMed 34554208

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AG-120 in people with Advanced Cholangiocarcinoma and Metastatic Cholangiocarcinoma, run by Institut de Recherches Internationales Servier at 49 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, South Korea, Spain, United Kingdom, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC) (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02989857, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.

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