Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

NCT ID: NCT03773302

Last Updated: 2024-05-08

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-27

Study Completion Date

2023-03-02

Brief Summary

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Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.

Detailed Description

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Conditions

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Advanced Cholangiocarcinoma FGFR2 Gene Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Infigratinib (BGJ398) 125 mg

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Group Type EXPERIMENTAL

BGJ398

Intervention Type DRUG

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Gemcitabine + Cisplatin

Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.

Group Type ACTIVE_COMPARATOR

Gemcitabine

Intervention Type DRUG

Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Cisplatin

Intervention Type DRUG

Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Interventions

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BGJ398

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Intervention Type DRUG

Gemcitabine

Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Intervention Type DRUG

Cisplatin

Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Intervention Type DRUG

Other Intervention Names

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Infigratinib

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
* Have written documentation of local laboratory or central laboratory determination of a known or likely activating FGFR2 fusion/rearrangement from a sample collected before randomization
* Have an archival tumor tissue sample available with sufficient tumor content for FGFR2 fusion/rearrangement molecular testing by the central laboratory. However, if an archival tumor tissue sample is not available, or does not meet requirements for central testing a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Are able to swallow and retain oral medication
* Are willingness to avoid pregnancy or father children

Exclusion Criteria

* Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions

1. Prior neoadjuvant or adjuvant therapy is permitted if completed \> 6 months after the last dose of neoadjuvant or adjuvant therapy.
2. One cycle of gemcitabine-based chemotherapy for locally advanced or metastatic cholangiocarcinoma is permitted before randomization
* History of a liver transplant
* Received previously or currently is receiving treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor
* Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
* Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
* History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
* Current evidence of corneal or retinal disorder/keratopathy
* Receiving and continued treatment or are planning to receive agents or consuming foods that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration
* Clinically significant or uncontrolled cardiac disease
* Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
* Severe hearing loss
* Severe neuropathy
* History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment
* Pregnant or breastfeeding
* Have known microsatellite instability-high (MSI-H) disease and the decision is made by the treating investigator that an alternative, non-study therapy is warranted according to standard of care.
* Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients
* Have any contraindication to cisplatin or gemcitabine treatment according to local labeling or standard institutional practice.
* Have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
* Have received a live vaccine within 30 days before the first dose of study drug or are planning to receive a live vaccine during participation in this study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Helsinn Healthcare SA

INDUSTRY

Sponsor Role collaborator

QED Therapeutics, Inc., a Bridgebio company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_DIRECTOR

QED Therapeutics

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

St. Joseph Heritage Healthcare

Fullerton, California, United States

Site Status

USC Norris Cancer Center

Los Angeles, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

Florida Hospital Medical Group

Orlando, Florida, United States

Site Status

UF Health Cancer Center at Orlando Health

Orlando, Florida, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute

Frederick, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center

Detroit, Michigan, United States

Site Status

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Levine Cancer Institute - Charlotte

Charlotte, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Charleston Oncology

Charleston, South Carolina, United States

Site Status

Parkland Health and Hospital System

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Chris O'Brien Lifehouse Hospital

Camperdown, New South Wales, Australia

Site Status

Blacktown Hospital

Darlinghurst, New South Wales, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Monash Medical Centre

Bentleigh East, Victoria, Australia

Site Status

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status

St John of God Hospital Subiaco

Subiaco, Western Australia, Australia

Site Status

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Site Status

Grand Hopital de Charleroi

Charleroi, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

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Ottawa Hospital

Ottawa, Ontario, Canada

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St. Josephs Health Centre

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Peking University People's Hospital

Beijing, , China

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

Hunan Cancer Hospital

Changsha, , China

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Guangzhou First People's Hospital

Guangzhou, , China

Site Status

Hubei Cancer Hospital

Hubei, , China

Site Status

Liaoning Cancer Hospital & Institute

Shenyang, , China

Site Status

The First Affiliated Hospital, Sun Yat-sen University

Zhongshan, , China

Site Status

Hopital Henri Mondor

Créteil, Val-de-Marne, France

Site Status

CHRU Dijon

Dijon, , France

Site Status

Centre Georges-Francois Leclerc

Dijon, , France

Site Status

Hopital Claude Huriez Rue Michel Polonovski (CHRU) Lille

Lille, , France

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Groupement Hospitalier Edouard Herriot

Lyon, , France

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Hopital Nord Franche-Comte

Montbéliard, , France

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Groupe Hospitalier Archet I Et II

Nice, , France

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Hopital Cochin

Paris, , France

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Hôpital Saint Antoine

Paris, , France

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L'Institut Mutualiste Montsouris

Paris, , France

Site Status

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, Germany

Site Status

Klinikum rechts der Isar der Technischen Universität München

München, Bavaria, Germany

Site Status

Klinikum Dortmund gGmbH

Dortmund, , Germany

Site Status

University Clinic Heidelberg

Heidelberg, , Germany

Site Status

Azienda Socio Sanitaria Territoriale di Cremona (ASST)

Cremona, , Italy

Site Status

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST

Meldola, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Istituto Oncologico Veneto - I.R.C.C.S.

Padua, , Italy

Site Status

Policlinico Universitario Campus Biomedico Di Roma

Roma, , Italy

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Hospital Beatriz Angelo

Loures, Lisbon District, Portugal

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Hospital Garcia de Orta

Almada, , Portugal

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Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, , Portugal

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Instituto Português de Oncologia Francisco Gentil Centro Regional de Oncologia de Coimbra EPE

Coimbra, , Portugal

Site Status

Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, , Portugal

Site Status

Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisbon, , Portugal

Site Status

Hospital CUF Descobertas

Lisbon, , Portugal

Site Status

Centro Hospitalar do Porto - Hospital de Santo António

Porto, , Portugal

Site Status

Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, , Portugal

Site Status

Centro Hospitalar de São João, E.P.E.

Porto, , Portugal

Site Status

Hospital Oncologico, Puerto Rico Medical Center

Rio Piedras, , Puerto Rico

Site Status

Pusan National University Hospital

Pusan, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

SMG - SNU Boramae Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Severance Hospital Yonsei University Health System

Seoul, , South Korea

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The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

Hospital Universitario Virgen Macarena

Seville, Andalusia, Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, Aragon, Spain

Site Status

Complejo Asistencial Universitario de Salamanca - Hospital Clinico

Salamanca, Castille and León, Spain

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, Catalonia, Spain

Site Status

Instituto Catalan de Oncologio ICO I'Hospitalet

Barcelona, Catalonia, Spain

Site Status

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

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Hospital Universitario Ramon y Cajal

Madrid, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, , Spain

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Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status

National Cheng Kung University Hospital

Tainan City, Tainan, Taiwan

Site Status

National Taiwan University Hospital - YunLin Branch

Huwei, , Taiwan

Site Status

Chang Gung Memorial Hospital - Kaohsiung

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

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Chi Mei Hospital, Liouying

Tainan City, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital, Linkou

Taoyuan, , Taiwan

Site Status

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, Changwat Songkhla, Thailand

Site Status

Chulalongkorn University

Bangkok, , Thailand

Site Status

Ramathibodi Hospital Mahidol University

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiang Mai, , Thailand

Site Status

Srinagarind Hospital

Khon Kaen, , Thailand

Site Status

Naresuan University

Phitsanulok, , Thailand

Site Status

Nottingham City Hospital

Nottingham, Nottinghamshire, United Kingdom

Site Status

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Site Status

Guys Hospital

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust - PPDS

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada China France Germany Italy Portugal Puerto Rico South Korea Spain Taiwan Thailand United Kingdom

References

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Makawita S, K Abou-Alfa G, Roychowdhury S, Sadeghi S, Borbath I, Goyal L, Cohn A, Lamarca A, Oh DY, Macarulla T, T Shroff R, Howland M, Li A, Cho T, Pande A, Javle M. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.

Reference Type DERIVED
PMID: 32580579 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-004004-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

QBGJ398-301

Identifier Type: -

Identifier Source: org_study_id

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