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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02989857
Recruitment Status : Active, not recruiting
First Posted : December 12, 2016
Last Update Posted : October 11, 2019
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief Summary:
Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of orally administered AG-120. Subjects, all personnel involved in the evaluation of subjects' response to treatment (e.g., Investigators, study coordinators, study pharmacists), and designated Sponsor team members will be blinded to study treatment. Subjects are required to have a histologically-confirmed diagnosis of 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. Subjects 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 subjects 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: AG-120 matched placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 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 : January 2017
Actual Primary Completion Date : January 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: AG-120 experimental study drug
AG-120, 500mg daily continuous dosing
Drug: AG-120
Placebo Comparator: AG-120 matched placebo
AG-120 matched placebo, daily continuous dosing. Subjects who experience disease progression and were receiving placebo, will be allowed to cross-over and receive AG-120
Drug: AG-120 matched placebo

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 26 weeks, on average ]

Secondary Outcome Measures :
  1. Adverse Event (AE) and Serious Adverse Event (SAE) analysis [ Time Frame: Up to 26 weeks, on average ]
  2. Overall Survival (OS) [ Time Frame: Up to 52 weeks, on average ]
  3. Overall Response Rate (ORR) [ Time Frame: Up to 26 weeks, on average ]
  4. Quality of Life (QOL) [ Time Frame: Up to 52 weeks, on average ]
    Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-C30

  5. Quality of Life (QOL) [ Time Frame: Up to 52 weeks, on average ]
    Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-Bil21

  6. Quality of Life (QOL) [ Time Frame: Up to 52 weeks, on average ]
    Method of assessment will be questionnaires. Questionnaire: PGI-C/PGI-S

  7. Health Economic Outcomes [ Time Frame: Up to 26 weeks, on average ]
    Method of assessment will be questionnaires. Questionnaire: EuroQOL EQ-5D-5L

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

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 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 RECIST v1.1. Subjects 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). Subjects must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced cholangiocarcinoma. Subjects 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. Subjects 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02989857

  Hide Study Locations
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United States, Arizona
Mayo Cancer Center
Scottsdale, Arizona, United States
United States, California
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
United States, Florida
Mayo Cancer Center
Jacksonville, Florida, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
University of Chicago Medical Center
Chicago, Illinois, United States
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Mayo Cancer Center
Rochester, Minnesota, United States
United States, Missouri
Washington University
Saint Louis, Missouri, United States
United States, New York
Columbia University
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
United States, South Carolina
Gibbs Cancer Center
Spartanburg, South Carolina, United States
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
United States, Texas
University of Texas, SouthWestern
Dallas, Texas, United States
UT MD Anderson Cancer Center
Houston, Texas, United States
United States, Utah
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States
United States, Wisconsin
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
Milano, Italy
Istituto Clinico Humanitas
Rozzano, Italy
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
National Cancer Center
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Seoul, St. Mary's Hospital
Seoul, Korea, Republic of
Yonsei University Severance Hospital
Seoul, Korea, Republic of
Hospital Vall d'Hebrón
Barcelona, Spain
Centro Integral Oncologico Clara Campal
Madrid, Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Marques de Valdecilla
Santander, Spain
United Kingdom
St. James University Hospital
Leeds, United Kingdom
Liverpool Cancer Center
Liverpool, United Kingdom
The Royal Free Hospital
London, United Kingdom
University College London Hospitals
London, United Kingdom
The Christie NHS Foundation Trust, the Christie Hospital
Manchester, United Kingdom
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
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Study Chair: Medical Affairs Agios Pharmaceuticals, Inc. Agios Pharmaceuticals, Inc.

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Responsible Party: Agios Pharmaceuticals, Inc. Identifier: NCT02989857     History of Changes
Other Study ID Numbers: AG120-C-005
First Posted: December 12, 2016    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Agios Pharmaceuticals, Inc.:
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs