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

• ClinicalTrials.gov Identifier: NCT02989857
• Recruitment Status: Completed
• First Posted: December 12, 2016
• Results First Posted: April 13, 2022
• Last Update Posted: January 17, 2023
• Sponsor: Institut de Recherches Internationales Servier
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma	Drug: AG-120; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients randomized in a 2:1 allocation (AG-120 vs Placebo)
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 20, 2017
• Actual Primary Completion Date: January 31, 2019
• Actual Study Completion Date: May 17, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AG-120; Participants 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.	Drug: AG-120; Tablet administered orally; Other Name: Ivosidenib
Placebo Comparator: Placebo; Participants 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.	Drug: Placebo; Tablet administered orally
Experimental: After Cross over to AG-120; Participants 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.	Drug: AG-120; Tablet administered orally; Other Name: Ivosidenib

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years) ]
   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.
2. Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events [ Time Frame: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years) ]
   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.
3. Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs [ Time Frame: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years) ]
   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.
4. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline ]
   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.
5. Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment [ Time Frame: From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years) ]
   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.
6. Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events [ Time Frame: 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) [ Time Frame: From date of randomization until the date of death due to any cause (Up to approximately 2 years) ]
   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.
8. Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1 [ Time Frame: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years) ]
   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.
9. ORR as Assessed by the IRC Per RECIST v1.1 [ Time Frame: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years) ]
   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.
10. Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years) ]
    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.
11. DOR as Assessed by the IRC Per RECIST v1.1 [ Time Frame: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years) ]
    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.
12. Time to Response (TTR) as Assessed by the Investigator [ Time Frame: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years) ]
    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.
13. TTR as Assessed by the IRC Per RECIST v1.1 [ Time Frame: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years) ]
    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.
14. PFS as Determined by Investigator [ 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) ]
    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.
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 [ Time Frame: Cycle 2 Day 1 and Cycle 3 Day 1 ]
    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.
16. Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21) [ Time Frame: Cycle 2 Day 1 and Cycle 3 Day 1 ]
    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).
17. Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C) [ Time Frame: Cycle 2 Day 1 and Cycle 3 Day 1 ]
    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.
18. Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S) [ Time Frame: Cycle 2 Day 1 and Cycle 3 Day 1 ]
    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.
19. Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response [ Time Frame: Cycle 3 Day 1 ]
    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.
20. Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score [ Time Frame: Cycle 3 Day 1 ]
    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).
21. Maximum Observed Plasma Concentration (Cmax) of AG-120 [ Time Frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
22. Time to Reach Maximal Plasma Concentration (Tmax) of AG-120 [ Time Frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
23. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) [ Time Frame: Post-dose of Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
24. Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4) [ Time Frame: Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
25. Accumulation Ratio Based on AUC0-4 (Racc AUC0-4) [ Time Frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
26. Accumulation Ratio Based on Cmax (Racc Cmax) [ Time Frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days) ]
    Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
27. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value) [ Time Frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    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.
28. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4 [ Time Frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    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.
29. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4 [ Time Frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days) ]
    %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.
30. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough [ Time Frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days) ]
    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.
31. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough [ Time Frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days) ]
    %BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be ≥18 years of age.
2. 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.
3. 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).
4. Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
5. Have an expected survival of ≥3 months.
6. 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.
7. 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.

Exclusion criteria:

1. Received a prior IDH inhibitor.
2. 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.
3. Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.
4. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.
5. 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.

Contacts and Locations

Locations

United States, Arizona

Mayo Cancer Center

Scottsdale, Arizona, United States, 85054

United States, California

City of Hope Cancer Center

Duarte, California, United States, 91010

University of California, Irvine

Irvine, California, United States, 92868

University of Southern California

Los Angeles, California, United States, 90033

University of California, San Francisco

San Francisco, California, United States, 94158

United States, Florida

Mayo Cancer Center

Jacksonville, Florida, United States, 32224

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Cancer Center

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10021

Columbia University

New York, New York, United States, 10032

United States, Ohio

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, South Carolina

Gibbs Cancer Center

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

University of Texas, SouthWestern

Dallas, Texas, United States, 75390

UT MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

United States, Wisconsin

University of Wisconsin, Carbone Cancer Center

Madison, Wisconsin, United States, 53792

France

Universite de Franche-Comte

Besançon, France, 25000

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

Bordeaux, France, 33076

Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

Rennes, France, 35042

Institut Gustave Roussy

Villejuif, France, 94805

Italy

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

Candiolo, Italy, 10060

Istituto Scientifico Universitario San Raffaele

Milano, Italy, 20127

Istituto Clinico Humanitas

Rozzano, Italy, 20089

Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Yonsei University Severance Hospital

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Seoul, St. Mary's Hospital

Seoul, Korea, Republic of, 06591

National Cancer Center

Seoul, Korea, Republic of, 10408

Spain

Hospital Vall d'Hebrón

Barcelona, Spain, 08035

Hospital General Universitario Gregorio Marañón

Madrid, Spain, 28007

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Centro Integral Oncologico Clara Campal

Madrid, Spain, 28050

Hospital Universitario Marques de Valdecilla

Santander, Spain, 39008

United Kingdom

St. James University Hospital

Leeds, United Kingdom, LS16 6QB

Liverpool Cancer Center

Liverpool, United Kingdom, CH63 4JY

University College London Hospitals

London, United Kingdom, NW1 2PG

The Royal Free Hospital

London, United Kingdom, NW3 2QG

The Christie NHS Foundation Trust, the Christie Hospital

Manchester, United Kingdom, M20 4QL

Sponsors and Collaborators

Institut de Recherches Internationales Servier

Investigators

• Study Chair: Medical Affairs Servier Pharmaceuticals LLC; Servier Pharmaceuticals, LLC

  Study Documents (Full-Text)

Documents provided by Servier ( Institut de Recherches Internationales Servier ):

Study Protocol: Protocol v6  [PDF] March 5, 2019

Study Protocol: Protocol v7  [PDF] June 23, 2021

Statistical Analysis Plan  [PDF] April 1, 2019

More Information

Study Data/Documents: Individual Participant Data Set 

Study Protocol 

Statistical Analysis Plan 

Informed Consent Form 

Clinical Study Report 

Study-level clinical trial data 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Erratum In: Lancet Oncol. 2020 Oct;21(10):e462. Lancet Oncol. 2024 Feb;25(2):e61.

• Responsible Party: Institut de Recherches Internationales Servier
• ClinicalTrials.gov Identifier: NCT02989857
• Other Study ID Numbers: AG120-C-005
• First Posted: December 12, 2016
• Results First Posted: April 13, 2022
• Last Update Posted: January 17, 2023
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

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 Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (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.
• URL: https://clinicaltrials.servier.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Servier ( Institut de Recherches Internationales Servier ):

IDH1

Additional relevant MeSH terms:

Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ivosidenib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action