A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
- Conditions
- Unresectable CholangiocarcinomaMetastatic Cholangiocarcinoma
- Interventions
- Registration Number
- NCT03656536
- Lead Sponsor
- Incyte Corporation
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 167
- Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
- Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
- Eastern Cooperative Oncology Group performance status 0 to 1.
- Documented FGFR2 rearrangement.
- Willingness to avoid pregnancy or fathering children.
- Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin]).
- Child-Pugh B and C.
- Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
- Concurrent anticancer therapy, other than the therapies being tested in this study.
- Participant is a candidate for potentially curative surgery.
- Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
- Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
- Known central nervous system (CNS) metastases or history of uncontrolled seizures.
- Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
- Laboratory values at screening outside the protocol-defined range.
- History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
- Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
- Clinically significant or uncontrolled cardiac disease.
- History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
- Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
- Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
- Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
- Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pemigatinib Pemigatinib - Gemcitabine + Cisplatin Cisplatin Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib. Gemcitabine + Cisplatin Gemcitabine Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.
- Primary Outcome Measures
Name Time Method Progression-free survival Up to approximately 12 months Defined as the time from date of randomization until date of disease progression (according to Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1 and assessed by an independent central reviewer (ICR)) or death, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Overall survival Up to approximately 12 months Defined as the time from date of randomization until death due to any cause.
Disease control rate Up to approximately 12 months Defined as the proportion of participants who achieved best overall response of CR, PR, or stable disease (SD) per RECIST v1.1 as assessed by an ICR.
Duration of response Up to approximately 12 months Defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression by an ICR per RECIST v1.1 or death, whichever occurs first.
Quality of Life impact as assessed by the EORTC QLQ-BIL21 questionnaire Up to 12 months Overall response rate Up to approximately 12 months Defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by an ICR.
Number of treatment-emergent adverse events Up to approximately 12 months Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
Quality of Life impact as assessed by the EQ-5D-3L questionnaire Up to 12 months Quality of Life impact as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire Up to 12 months
Trial Locations
- Locations (214)
Parkview Research Center
🇺🇸Fort Wayne, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Baylor Scott and White Research Institute
🇺🇸Dallas, Texas, United States
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
White Plains Hospital
🇺🇸White Plains, New York, United States
Xinhua Hospital
🇨🇳SHanghai, China
Centre Hospitalier Universitaire de Bordeaux - Hospital Haut-Leveque
🇫🇷Pessac Cedex, France
Hospital de La Miletrie
🇫🇷Poitiers Cedex, France
Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
🇫🇷Saint Herblain, France
University Medical Center Rwth Aachen
🇩🇪Aachen, Germany
Chu Vandoeuvre-Les-Nancy Hopital Brabois
🇫🇷Vandoeuvre Les Nancy, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitatsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Universitatsklinikum Koln
🇩🇪Koln, Germany
University Hospital Grosshadern Munich
🇩🇪Munich, Germany
Soroka University Medical Center
🇮🇱Beer-sheva, Israel
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Chiba Cancer Center
🇯🇵Chiba-shi, Japan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Kobe University Hospital
🇯🇵Kobe-shi, Japan
Kyoto University Hospital
🇯🇵Kyoto-shi, Japan
Nho Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
University Hospital Coventry and Warwickshire
🇬🇧Coventry, United Kingdom
The Royal Marsden Nhs Foundation Trust - Chelsea
🇬🇧London, United Kingdom
The Royal Marsden Nhs Foundation Trust - Sutton
🇬🇧Sutton, United Kingdom
Houston Methodist Research Institute
🇺🇸Houston, Texas, United States
Comprehensive Cancer Centers of Nevada-Twain
🇺🇸Las Vegas, Nevada, United States
Kunming 1St People'S Hospital
🇨🇳Kunming, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Barbara Ann Karmanos Cancer Hospital
🇺🇸Detroit, Michigan, United States
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
🇮🇹Milano, Italy
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
🇮🇹Milan, Italy
European Institute of Oncology
🇮🇹Milan, Italy
A.O.U. Di Modena - Policlinico
🇮🇹Modena, Italy
Iov - Istituto Oncologico Veneto Irccs
🇮🇹Padova, Italy
Presidio Ospedaliero Pescara
🇮🇹Pescara, Italy
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Italy
Fondazione Policlinico Universitario Agostino Gemelli Irccs
🇮🇹Roma, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Marin Cancer Care
🇺🇸Greenbrae, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Mayo Clinic-Florida
🇺🇸Jacksonville, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Mount Sinai Medical Center Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Johns Hopkins Oncology Center
🇺🇸Baltimore, Maryland, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Institute
🇺🇸Farmington Hills, Michigan, United States
Icahn School of Medicine At Mount Sinai
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Providence Portland Med. Ctr
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Ordensklinikum Krankenhaus Der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Landeskrankenhaus Universitatsklinikum Graz
🇦🇹Graz, Austria
West Virginia University Cancer Institute
🇺🇸Morgantown, West Virginia, United States
Innsbruck University Hospital
🇦🇹Innsbruck, Austria
Salzburger Universitatsklinikum
🇦🇹Salzburg, Austria
Universitair Ziekenhuis Brussel
🇧🇪Bruxelles, Belgium
Landeskrankenhaus Steyr
🇦🇹Steyr, Austria
Allgemeines Krankenhaus Der Stadt Wien
🇦🇹Vienna, Austria
Ulb Hospital Erasme
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Hospital de Jolimont
🇧🇪Haine-st-paul, Belgium
Chu Ucl Namur University Hospital Mont-Godinne
🇧🇪Yvoir, Belgium
Az Groeninge Campus Kennedylaan
🇧🇪Kortrijk, Belgium
Cancercare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Peking Union Medical College Hospital
🇨🇳Beijing, China
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
West China Hospital Sichuan University
🇨🇳Chengdu, China
Shulan Hangzhou Hospital Co Ltd
🇨🇳Hangzhou, China
Sun Yat-Sen Memorial Hospital Sun Yat-Sen University
🇨🇳Guangzhou, China
Heilongjiang Province Cancer Hospital
🇨🇳Harbin, China
University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)
🇨🇳Hefei, China
The Affiliated Hospital of Qingdao University
🇨🇳Shandong, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Jiangsu Province Hospital
🇨🇳Nanjing, China
Sichuan Cancer Hospital
🇨🇳Sichuan, China
Tianjin Medical University Cancer Institute Hospital
🇨🇳Tianjin, China
Tongji Hospital Huazhong University of Science and Technology
🇨🇳Wuhan, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Northern Jiangsu Peoples Hospital
🇨🇳Yangzhou, China
Chu Besancon Hospital Jean Minjoz
🇫🇷Besançon, France
Herlev Og Gentofte Hospital
🇩🇰Herlev, Denmark
Docrates Cancer Center
🇫🇮Helsinki, Finland
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Institut Sainte Catherine
🇫🇷Avignon Cedex 9, France
Tampere University Hospital
🇫🇮Tampere, Finland
Institut Bergonie
🇫🇷Bordeaux Cedex, France
Hopital Beaujon
🇫🇷Clichy, France
Hopital Prive Jean Mermoz
🇫🇷Lyon Cedex 08, France
Chu Hopital de La Timone
🇫🇷Marseille Cedex 5, France
Chu de Limoges - Hospital Dupuytren
🇫🇷Limoges Cedex, France
Centre Hospitalier Universitaire de Nantes
🇫🇷Nantes, France
Centre Antoine Laccassagne
🇫🇷Nice Cedex 02, France
Hospital Universitaire Pitie-Salpetriere
🇫🇷Paris Cedex 13, France
Hopital Europeen Georges Pompidou (Hegp)
🇫🇷Paris Cedex 15, France
Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume
🇫🇷Rouen Cedex, France
University Hospital of Saint Etienne
🇫🇷Saint Etienne, France
Chu Toulouse Hopital Rangueil
🇫🇷Toulouse Cedex 9, France
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
🇩🇪Berlin, Germany
Universitatsklinikum Bonn Aoer
🇩🇪Bonn, Germany
University Clinic Carl Gustav Carus Technical University Dresden
🇩🇪Dresden, Germany
Klinikum Der Johann Wolfgang Goethe University
🇩🇪Frankfurt Am Main, Germany
University Medical Center Freiburg
🇩🇪Freiburg, Germany
Hannover Medical School
🇩🇪Hannover, Germany
Universitaetsklinikum Des Saarlandes
🇩🇪Homburg / Saar, Germany
Klinikum Ludwigsburg
🇩🇪Ludwigsburg, Germany
Universitatsklinikum Leipzig Aor
🇩🇪Leipzig, Germany
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
🇩🇪Mainz, Germany
Otto-Von-Guericke-Universitat Magdeburg
🇩🇪Magdeburg, Germany
Klinikum Nuernberg
🇩🇪Nuernberg, Germany
Universitaetsklinikum in Tubingen
🇩🇪Tubingen, Germany
University Hospital Tuebingen
🇩🇪Tubingen, Germany
Universitatkinikums Ulm
🇩🇪ULM, Germany
St. Vincent'S University Hospital
🇮🇪Dublin 4, Ireland
Rambam Health Care Campus
🇮🇱Haifa, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Ospedale Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Azienda Ospedaliero Universitaria Delle Marche
🇮🇹Ancona, Italy
Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
🇮🇹Bari, Italy
Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo
🇮🇹Candiolo, Italy
Ospedale Degli Infermi - Faenza
🇮🇹Faenza, Italy
Presidio Ospedaliero Garibaldi Nesima
🇮🇹Catania, Italy
Irccs Azienda Ospedaliera Universitaria San Martino
🇮🇹Genova, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milan, Italy
Istituto Nazionale Tumori Irccs Fondazione Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
🇮🇹Orbassano, Italy
Universita Degli Studi Della Campania Luigi Vanvitelli U.O.C. Oncologia Medica
🇮🇹Napoli, Italy
Universita Campus Bio Medico Di Roma
🇮🇹Rome, Italy
Istituto Nazionale Tumori Regina Elena Irccs
🇮🇹Roma, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Rome, Italy
Centro Ricerche Cliniche Di Verona (Crc)
🇮🇹Verona, Italy
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
🇮🇹Siena, Italy
San Bartolo Hospital
🇮🇹Vicenza, Italy
University of Tokyo Hospital
🇯🇵Bunkyo, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Hyogo College of Medicine Hospital
🇯🇵Hyogo, Japan
Hiroshima University Hospital
🇯🇵Hiroshima-shi, Japan
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Teikyo University Hospital
🇯🇵Itabashi-ku, Japan
Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Kyorin University Hospital
🇯🇵Mitaka-shi, Japan
Kindai University Hospital
🇯🇵Osakasayama City, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Toyama University Hospital
🇯🇵Toyama-shi, Japan
Yamaguchi University Hospital
🇯🇵UBE, Japan
Yokohama City University Medical Center
🇯🇵Yokohama-shi, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Oita University Hospital
🇯🇵Yufu-shi, Japan
Amsterdam University Medical Centre
🇳🇱Amsterdam, Netherlands
Maastricht Umc+
🇳🇱Maastricht, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Umc Utrecht
🇳🇱Utrecht, Netherlands
Oslo University Hospital
🇳🇴Oslo, Norway
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Clinic Barcelona Main
🇪🇸Barcelona, Spain
Hospital Materno Teresa Herrera
🇪🇸La Coruña, Spain
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Hm Sanchinarro
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Clinica Universidad de Navarra (Cun)
🇪🇸Pamplona, Spain
HOSPITAL UNiVERSITARIO DONOSTIA
🇪🇸San Sebastian, Spain
Hospital Universitari Parc Tauli
🇪🇸Sabadell, Spain
Karolinska Institute Universitetssjukhuset Solna
🇸🇪Solna, Sweden
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Inselspital - Universitaetsspital Bern
🇨🇭Bern, Switzerland
Universitatsspital Zurich
🇨🇭Zuerich, Switzerland
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
University College London Hospitals (Uclh)
🇬🇧London, United Kingdom
Kent Oncology Centre - Maidstone Hospital
🇬🇧Maidstone, United Kingdom
The Christie Nhs Foundation Trust
🇬🇧Manchester, United Kingdom
Riverside Regional Medical Center
🇺🇸Newport News, Virginia, United States
Klinikum Bremen-Nord
🇩🇪Bremen, Germany
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
McGill University Health Centre Research Institute
🇨🇦Montreal, Quebec, Canada
Nova Scotia Health Authority/Qeii Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Japan
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Georgetown University-Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
Universitaire Ziekenhuis Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Rabin Medical Center - Beilinson Hospital
🇮🇱Petach Tikva, Israel
Greenville Hospital System University Medical Center Institute For Translational Oncology Research
🇺🇸Greenville, South Carolina, United States
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States
Ochsner Clinic Foundation Ocf Ochsner Cancer Institute Oci
🇺🇸New Orleans, Louisiana, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Aurora Research Institute
🇺🇸Wauwatosa, Wisconsin, United States
Fujian Cancer Hospital
🇨🇳Fuzhou, China