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

NCT ID: NCT02989857

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2021-05-17

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.

Conditions

Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

AG-120

Intervention Type: DRUG

Tablet administered orally

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet administered orally

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.

Group Type: EXPERIMENTAL

AG-120

Intervention Type: DRUG

Tablet administered orally

Interventions

AG-120

Tablet administered orally

Intervention Type: DRUG

Placebo

Tablet administered orally

Intervention Type: DRUG

Other Intervention Names

Ivosidenib

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Affairs Servier Pharmaceuticals LLC

Role: STUDY_CHAIR

Servier Pharmaceuticals, LLC

Locations

Mayo Cancer Center

Scottsdale, Arizona, United States

City of Hope Cancer Center

Duarte, California, United States

University of California, Irvine

Irvine, California, United States

University of Southern California

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

Mayo Cancer Center

Jacksonville, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Cancer Center

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Columbia University

New York, New York, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Gibbs Cancer Center

Spartanburg, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas, SouthWestern

Dallas, Texas, United States

UT MD Anderson Cancer Center

Houston, Texas, United States

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

University of Wisconsin, Carbone Cancer Center

Madison, Wisconsin, United States

Universite de Franche-Comte

Besançon, , France

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

Bordeaux, , France

Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

Rennes, , France

Institut Gustave Roussy

Villejuif, , France

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

Candiolo, , Italy

Istituto Scientifico Universitario San Raffaele

Milan, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Seoul National University Hospital

Seoul, , South Korea

Yonsei University Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul, St. Mary's Hospital

Seoul, , South Korea

National Cancer Center

Seoul, , South Korea

Hospital Vall d'Hebrón

Barcelona, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

St. James University Hospital

Leeds, , United Kingdom

Liverpool Cancer Center

Liverpool, , United Kingdom

University College London Hospitals

London, , United Kingdom

The Royal Free Hospital

London, , United Kingdom

The Christie NHS Foundation Trust, the Christie Hospital

Manchester, , United Kingdom

Countries

United States; France; Italy; South Korea; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 32416072 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38278871 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34554208 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol v6

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Document Type: Study Protocol: Protocol v7

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Document Type: Statistical Analysis Plan

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Study Documents

Document Type: Individual Participant Data Set

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Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Document Type: Informed Consent Form

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Document Type: Clinical Study Report

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Document Type: Study-level clinical trial data

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Other Identifiers

AG120-C-005

Identifier Type: -

Identifier Source: org_study_id