Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
- Conditions
- Advanced CholangiocarcinomaFGFR2 Gene Mutation
- Interventions
- Registration Number
- NCT03773302
- Lead Sponsor
- QED Therapeutics, Inc.
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 48
- 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
-
Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions
- Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant therapy.
- 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
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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
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Clinically significant or uncontrolled cardiac disease
-
Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
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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
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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.
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Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients
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Have any contraindication to cisplatin or gemcitabine treatment according to local labeling or standard institutional practice.
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Have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Infigratinib (BGJ398) 125 mg BGJ398 Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off. Gemcitabine + Cisplatin Gemcitabine Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met. Gemcitabine + Cisplatin Cisplatin Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.
- Primary Outcome Measures
Name Time Method Progression-free Survival (Central Imaging Assessment) From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment. Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors \[RECIST\] v. 1.1) or death, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). DCR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR), confirmed complete response (CR) or stable disease (SD) or non-CR/non-PD before crossover.
Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive. OS by investigator assessment, defined as time from date of randomization until death due to any cause
Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment. Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). ORR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR) or confirmed complete response (CR) as assessed by BICR and the investigator according to RECIST v1.1 among patients with measurable disease at baseline
Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). BOR was defined as the best response a subject ever achieved after study treatment prior to crossover and any subsequent anticancer therapy, complete response (CR) and partial response (PR) were claimed only if the criteria for each were met at a subsequent time point at least 4 weeks apart. In the case of stable disease (SD), measurements must have met the SD criteria at least once post-baseline no less than 6 weeks from the randomization date.
Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). DOR is defined as the time from initiation of confirmed partial response (PR) or confirmed complete response (CR) to the time of confirmed progressive disease (PD) or death. If subjects do not reach PD or death before crossover, the DOR is censored at the last valid tumor assessment before crossover.
Number of Participants With Adverse Events (AEs) From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm). Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
Number of Participants With Serious Adverse Events (SAEs) From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm). Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
Trial Locations
- Locations (116)
Parkland Health and Hospital System
🇺🇸Dallas, Texas, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹Lisbon, Portugal
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan City, Taiwan
Maharaj Nakorn Chiang Mai Chiang Mai University
🇹🇭Chiang Mai, Thailand
Nottingham City Hospital
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Chulalongkorn University
🇹🇭Bangkok, Thailand
Centro Hospitalar E Universitário de Coimbra EPE
🇵🇹Coimbra, Portugal
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Hospital CUF Descobertas
🇵🇹Lisboa, Portugal
Ramathibodi Hospital Mahidol University
🇹🇭Bangkok, Thailand
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
St John of God Hospital Subiaco
🇦🇺Subiaco, Western Australia, Australia
Hopital Henri Mondor
🇫🇷Créteil, Val-de-Marne, France
Guangzhou First People's Hospital
🇨🇳Guangzhou, China
Hubei Cancer Hospital
🇨🇳Hubei, China
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padova, Italy
Klinikum Dortmund gGmbH
🇩🇪Dortmund, Germany
Hopital Cochin
🇫🇷Paris, France
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
L'Institut Mutualiste Montsouris
🇫🇷Paris, France
Ajou University Hospital
🇰🇷Suwon-si, Korea, Republic of
Chris O'Brien Lifehouse Hospital
🇦🇺Camperdown, New South Wales, Australia
Complejo Asistencial Universitario de Salamanca - Hospital Clinico
🇪🇸Salamanca, Castilla Y Leon, Spain
Policlinico Universitario Campus Biomedico Di Roma
🇮🇹Roma, Italy
Monash Medical Centre
🇦🇺Bentleigh East, Victoria, Australia
CHRU Dijon
🇫🇷Dijon, France
Hôpital Saint Antoine
🇫🇷Paris, France
Groupement Hospitalier Edouard Herriot
🇫🇷Lyon, France
St. Josephs Health Centre
🇨🇦Toronto, Ontario, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
University Clinic Heidelberg
🇩🇪Heidelberg, Germany
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Centre Georges-Francois Leclerc
🇫🇷Dijon, France
Centro Hospitalar de São João, E.P.E.
🇵🇹Porto, Portugal
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
🇮🇹Meldola, Italy
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Garcia de Orta
🇵🇹Almada, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
🇵🇹Porto, Portugal
National Cheng Kung University Hospital
🇨🇳Tainan City, Tainan, Taiwan
Hospital Oncologico, Puerto Rico Medical Center
🇵🇷Rio Piedras, Puerto Rico
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Andalucia, Spain
Hospital Universitario HM Sanchinarro - CIOCC
🇪🇸Madrid, Spain
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Hospital Beatriz Angelo
🇵🇹Loures, Lisboa, Portugal
Instituto Português de Oncologia Francisco Gentil Centro Regional de Oncologia de Coimbra EPE
🇵🇹Coimbra, Portugal
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Centro Hospitalar do Porto - Hospital de Santo António
🇵🇹Porto, Portugal
Chang Gung Memorial Hospital - Kaohsiung
🇨🇳Kaohsiung, Taiwan
Pusan National University Hospital
🇰🇷Pusan, Korea, Republic of
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
China Medical University Hospital
🇨🇳Taichung City, Taiwan
Songklanagarind Hospital, Prince of Songkla University
🇹🇭Hat Yai, Songkla, Thailand
Naresuan University
🇹🇭Phitsanulok, Thailand
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
National Taiwan University Hospital - YunLin Branch
🇨🇳Huwei, Taiwan
Chi Mei Hospital, Liouying
🇨🇳Tainan, Taiwan
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Bebington, Wirral, United Kingdom
The Christie NHS Foundation Trust - PPDS
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Zhongshan, China
Peking University People's Hospital
🇨🇳Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
Klinikum rechts der Isar der Technischen Universität München
🇩🇪München, Bayern, Germany
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Florida Hospital Medical Group
🇺🇸Orlando, Florida, United States
Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute
🇺🇸Frederick, Maryland, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center
🇺🇸Detroit, Michigan, United States
Levine Cancer Institute - Charlotte
🇺🇸Charlotte, North Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Blacktown Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Peking University Third Hospital
🇨🇳Beijing, China
Hunan Cancer Hospital
🇨🇳Changsha, China
Hopital Claude Huriez Rue Michel Polonovski (CHRU) Lille
🇫🇷Lille, France
Azienda Socio Sanitaria Territoriale di Cremona (ASST)
🇮🇹Cremona, Italy
Groupe Hospitalier Archet I Et II
🇫🇷Nice, France
Hopital Nord Franche-Comte
🇫🇷Montbéliard, France
Universitätsklinikum Tübingen
🇩🇪Tübingen, Baden-Wurttemberg, Germany
SMG - SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Instituto Catalan de Oncologio ICO I'Hospitalet
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Cataluna, Spain
Hospital Universitario Vall d'Hebrón - PPDS
🇪🇸Barcelona, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Aragon, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Guys Hospital
🇬🇧London, United Kingdom
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
University Medical Center - New Orleans
🇺🇸New Orleans, Louisiana, United States
Charleston Oncology
🇺🇸Charleston, South Carolina, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada