A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma

Metastatic Cholangiocarcinoma Clinical Trial

— FIGHT-302  

Official title:

A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study 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 (FIGHT-302)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03656536
• Other study ID #: INCB 54828-302
• Status: Recruiting
• Phase: Phase 3
• Start date: June 3, 2019
• Est. completion date: July 27, 2028

Study information

• Verified date: May 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 434
• Est. completion date: July 27, 2028
• Est. primary completion date: October 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Metastatic Cholangiocarcinoma
• Unresectable Cholangiocarcinoma

Intervention

Drug:
• Pemigatinib
Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule (a cycle is 3 weeks).
• Gemcitabine
Gemcitabine 1000 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.
• Cisplatin
Cisplatin 25 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Universitatsklinikum Graz	Graz
Austria	Innsbruck University Hospital	Innsbruck
Austria	Ordensklinikum Krankenhaus Der Barmherzigen Schwestern Linz	Linz
Austria	Salzburger Universitatsklinikum	Salzburg
Austria	Landeskrankenhaus Steyr	Steyr
Austria	Allgemeines Krankenhaus Der Stadt Wien	Vienna
Belgium	Ulb Hospital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Hospital de Jolimont	Haine-st-paul
Belgium	Az Groeninge Campus Kennedylaan	Kortrijk
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Belgium	Chu Ucl Namur University Hospital Mont-Godinne	Yvoir
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Nova Scotia Health Authority/Qeii Health Sciences Centre	Halifax	Nova Scotia
Canada	McGill University Health Centre Research Institute	Montreal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	Cancercare Manitoba	Winnipeg	Manitoba
China	Peking Union Medical College Hospital	Beijing
China	West China Hospital Sichuan University	Chengdu
China	Fujian Cancer Hospital	Fuzhou
China	Sun Yat-Sen Memorial Hospital Sun Yat-Sen University	Guangdong
China	Sun Yat-Sen Memorial Hospital Sun Yat-Sen University	Guangzhou
China	Shulan Hangzhou Hospital Co Ltd	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	Heilongjiang Province Cancer Hospital	Harbin
China	University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)	Hefei
China	Kunming 1St People'S Hospital	Kunming
China	Jiangsu Province Hospital	Nanjing
China	The Affiliated Hospital of Qingdao University	Shandong
China	Xinhua Hospital	SHanghai
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Sichuan Cancer Hospital	Sichuan
China	Tianjin Medical University Cancer Institute Hospital	Tianjin
China	Hubei Cancer Hospital	Wuhan
China	Tongji Hospital Huazhong University of Science and Technology	Wuhan
China	Northern Jiangsu Peoples Hospital	Yangzhou
Denmark	Herlev Og Gentofte Hospital	Herlev
Finland	Docrates Cancer Center	Helsinki
Finland	Helsinki University Central Hospital	Helsinki
Finland	Tampere University Hospital	Tampere
France	Institut Sainte Catherine	Avignon Cedex 9
France	Chu Besancon Hospital Jean Minjoz	Besançon
France	Institut Bergonie	Bordeaux Cedex
France	Hopital Beaujon	Clichy
France	Chu de Limoges - Hospital Dupuytren	Limoges Cedex
France	Hopital Prive Jean Mermoz	Lyon Cedex 08
France	Chu Hopital de La Timone	Marseille Cedex 5
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	Centre Hospitalier Universitaire de Bordeaux - Hospital Haut-Leveque	Pessac Cedex
France	Hospital de La Miletrie	Poitiers Cedex
France	Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume	Rouen Cedex
France	University Hospital of Saint Etienne	Saint Etienne
France	Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau	Saint Herblain
France	Chu Toulouse Hopital Rangueil	Toulouse Cedex 9
France	Chu Vandoeuvre-Les-Nancy Hopital Brabois	Vandoeuvre Les Nancy
France	Institut Gustave Roussy	Villejuif Cedex
Germany	University Medical Center Rwth Aachen	Aachen
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin
Germany	Universitatsklinikum Bonn Aoer	Bonn
Germany	Klinikum Bremen-Nord	Bremen
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	Asklepios Klinik Altona	Hamburg
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	Hannover Medical School	Hannover
Germany	Universitaetsklinikum Des Saarlandes	Homburg / Saar
Germany	Universitatsklinikum Koln	Koln
Germany	Universitatsklinikum Leipzig Aor	Leipzig
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Otto-Von-Guericke-Universitat Magdeburg	Magdeburg
Germany	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz
Germany	University Hospital Grosshadern Munich	Munich
Germany	Klinikum Nuernberg	Nuernberg
Germany	Universitaetsklinikum in Tubingen	Tubingen
Germany	University Hospital Tuebingen	Tubingen
Germany	Universitatkinikums Ulm	ULM
Ireland	St. Vincent'S University Hospital	Dublin 4
Israel	Soroka University Medical Center	Beer-sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Delle Marche	Ancona
Italy	Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari	Bari
Italy	Ospedale Papa Giovanni Xxiii	Bergamo
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo	Candiolo
Italy	Presidio Ospedaliero Garibaldi Nesima	Catania
Italy	Ospedale Degli Infermi - Faenza	Faenza
Italy	Irccs Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milan
Italy	European Institute of Oncology	Milan
Italy	Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele	Milan
Italy	Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano	Milano
Italy	A.O.U. Di Modena - Policlinico	Modena
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Napoli
Italy	Universita Degli Studi Della Campania Luigi Vanvitelli U.O.C. Oncologia Medica	Napoli
Italy	Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano	Orbassano
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	Istituto Nazionale Tumori Regina Elena Irccs	Roma
Italy	Azienda Ospedaliera San Camillo Forlanini	Rome
Italy	Universita Campus Bio Medico Di Roma	Rome
Italy	Irccs Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte	Siena
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Italy	San Bartolo Hospital	Vicenza
Japan	University of Tokyo Hospital	Bunkyo
Japan	Chiba University Hospital	Chiba
Japan	Chiba Cancer Center	Chiba-shi
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Kyushu University Hospital	Fukuoka-shi
Japan	Hiroshima University Hospital	Hiroshima-shi
Japan	Hyogo College of Medicine Hospital	Hyogo
Japan	Kanazawa University Hospital	Ishikawa
Japan	Teikyo University Hospital	Itabashi-ku
Japan	Kobe University Hospital	Kobe-shi
Japan	Cancer Institute Hospital of Jfcr	Koto-ku
Japan	Kyoto University Hospital	Kyoto-shi
Japan	Nho Shikoku Cancer Center	Matsuyama-shi
Japan	Kyorin University Hospital	Mitaka-shi
Japan	Aichi Cancer Center Hospital	Nagoya-shi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Osaka International Cancer Institute	Osaka-shi
Japan	Kindai University Hospital	Osakasayama City
Japan	Saitama Cancer Center	Saitama
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Tohoku University Hospital	Sendai-shi
Japan	Jichi Medical University Hospital	Shimotsuke-shi
Japan	Keio University Hospital	Shinjuku-ku
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Osaka University Hospital	Suita-shi
Japan	Toyama University Hospital	Toyama-shi
Japan	Yamaguchi University Hospital	UBE
Japan	Wakayama Medical University Hospital	Wakayama
Japan	Kanagawa Cancer Center	Yokohama-shi
Japan	Yokohama City University Medical Center	Yokohama-shi
Japan	Oita University Hospital	Yufu-shi
Netherlands	Amsterdam University Medical Centre	Amsterdam
Netherlands	Maastricht Umc+	Maastricht
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Umc Utrecht	Utrecht
Norway	Oslo University Hospital	Oslo
Spain	Hospital Clinic Barcelona Main	Barcelona
Spain	Hospital Clinic Barcelona Main	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Materno Teresa Herrera	La Coruña
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Hm Sanchinarro	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Clinica Universidad de Navarra (Cun)	Pamplona
Spain	Hospital Universitari Parc Tauli	Sabadell
Spain	HOSPITAL UNiVERSITARIO DONOSTIA	San Sebastian
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital General Universitario de Valencia	Valencia
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Karolinska Institute Universitetssjukhuset Solna	Solna
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Universitatsspital Zurich	Zuerich
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	University Hospital Coventry and Warwickshire	Coventry
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	The Royal Marsden Nhs Foundation Trust - Chelsea	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	The Royal Marsden Nhs Foundation Trust - Sutton	Sutton
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor Scott and White Research Institute	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Karmanos Cancer Institute	Farmington Hills	Michigan
United States	Summit Medical Group	Florham Park	New Jersey
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Marin Cancer Care	Greenbrae	California
United States	Greenville Hospital System University Medical Center Institute For Translational Oncology Research	Greenville	South Carolina
United States	Houston Methodist Research Institute	Houston	Texas
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Mayo Clinic-Florida	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada-Twain	Las Vegas	Nevada
United States	Mount Sinai Medical Center Comprehensive Cancer Center	Miami Beach	Florida
United States	West Virginia University Cancer Institute	Morgantown	West Virginia
United States	Ochsner Clinic Foundation Ocf Ochsner Cancer Institute Oci	New Orleans	Louisiana
United States	Icahn School of Medicine At Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Riverside Regional Medical Center	Newport News	Virginia
United States	UC Irvine Medical Center	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Providence Portland Med. Ctr	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Georgetown University-Lombardi Comprehensive Cancer Center	Washington	District of Columbia
United States	Aurora Research Institute	Wauwatosa	Wisconsin
United States	The University of Kansas Cancer Center	Westwood	Kansas
United States	White Plains Hospital	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	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.	Up to approximately 12 months
Secondary	Overall response rate	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.	Up to approximately 12 months
Secondary	Overall survival	Defined as the time from date of randomization until death due to any cause.	Up to approximately 12 months
Secondary	Duration of response	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.	Up to approximately 12 months
Secondary	Disease control rate	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.	Up to approximately 12 months
Secondary	Number of treatment-emergent adverse events	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to approximately 12 months
Secondary	Quality of Life impact as assessed by the EQ-5D-3L questionnaire		Up to 12 months
Secondary	Quality of Life impact as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire		Up to 12 months
Secondary	Quality of Life impact as assessed by the EORTC QLQ-BIL21 questionnaire		Up to 12 months