Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
Advanced Cholangiocarcinoma, FGFR2 Gene Mutation
About this trial
This is an interventional treatment trial for Advanced Cholangiocarcinoma focused on measuring cholangiocarcinoma, unresectable cholangiocarcinoma, metastatic cholangiocarcinoma, fibroblast growth factor receptor inhibitor, FGFR2, FGFR2 gene fusions/translocations, BGJ398
Eligibility Criteria
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
- 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
- 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
Sites / Locations
- Banner MD Anderson Cancer Center
- University of Arizona
- University of Arkansas for Medical Sciences
- St. Joseph Heritage Healthcare
- USC Norris Cancer Center
- University of California Los Angeles
- Florida Hospital Medical Group
- UF Health Cancer Center at Orlando Health
- Northwestern Memorial Hospital
- University Medical Center - New Orleans
- Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute
- Massachusetts General Hospital
- Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center
- Cancer and Hematology Centers of Western Michigan
- William Beaumont Hospital
- NYU Langone Medical Center
- Memorial Sloan Kettering Cancer Center
- Levine Cancer Institute - Charlotte
- University of Cincinnati Medical Center
- Ohio State University Comprehensive Cancer Center
- Charleston Oncology
- Parkland Health and Hospital System
- University of Texas Southwestern Medical Center
- University of Texas MD Anderson Cancer Center
- Baylor College of Medicine
- Chris O'Brien Lifehouse Hospital
- Blacktown Hospital
- Royal Adelaide Hospital
- Monash Medical Centre
- Peninsula & South Eastern Haematology and Oncology Group
- St John of God Hospital Subiaco
- Cliniques Universitaires Saint-Luc
- Grand Hopital de Charleroi
- Universitair Ziekenhuis Antwerpen
- Cross Cancer Institute
- Ottawa Hospital
- St. Josephs Health Centre
- Jewish General Hospital
- Peking University People's Hospital
- Beijing Cancer Hospital
- Peking University Third Hospital
- Hunan Cancer Hospital
- Guangzhou First People's Hospital
- Hubei Cancer Hospital
- Liaoning Cancer Hospital & Institute
- The First Affiliated Hospital, Sun Yat-sen University
- Hopital Henri Mondor
- CHRU Dijon
- Centre Georges-Francois Leclerc
- Hopital Claude Huriez Rue Michel Polonovski (CHRU) Lille
- Groupement Hospitalier Edouard Herriot
- Hopital Nord Franche-Comte
- Groupe Hospitalier Archet I Et II
- Hopital Cochin
- Hôpital Saint Antoine
- L'Institut Mutualiste Montsouris
- Universitätsklinikum Tübingen
- Klinikum rechts der Isar der Technischen Universität München
- Klinikum Dortmund gGmbH
- University Clinic Heidelberg
- Azienda Socio Sanitaria Territoriale di Cremona (ASST)
- Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- ASST Grande Ospedale Metropolitano Niguarda
- Istituto Oncologico Veneto - I.R.C.C.S.
- Policlinico Universitario Campus Biomedico Di Roma
- Pusan National University Hospital
- Seoul National University Bundang Hospital
- SMG - SNU Boramae Medical Center
- Samsung Medical Center
- Seoul National University Hospital
- Severance Hospital Yonsei University Health System
- The Catholic University of Korea, Seoul St. Mary's Hospital
- Ajou University Hospital
- Hospital Beatriz Angelo
- Hospital Garcia de Orta
- Centro Hospitalar E Universitário de Coimbra EPE
- Instituto Português de Oncologia Francisco Gentil Centro Regional de Oncologia de Coimbra EPE
- Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
- Hospital CUF Descobertas
- Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
- Centro Hospitalar do Porto - Hospital de Santo António
- Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
- Centro Hospitalar de São João, E.P.E.
- Hospital Oncologico, Puerto Rico Medical Center
- Hospital Universitario Virgen Macarena
- Hospital Universitario Miguel Servet
- Complejo Asistencial Universitario de Salamanca - Hospital Clinico
- Hospital Universitario Germans Trias i Pujol
- Instituto Catalan de Oncologio ICO I'Hospitalet
- Hospital Universitario Vall d'Hebrón - PPDS
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario Ramon y Cajal
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- Hospital Universitario HM Sanchinarro - CIOCC
- Hospital Universitari i Politecnic La Fe de Valencia
- National Cheng Kung University Hospital
- National Taiwan University Hospital - YunLin Branch
- Chang Gung Memorial Hospital - Kaohsiung
- China Medical University Hospital
- Chi Mei Hospital, Liouying
- Taipei Veterans General Hospital
- National Taiwan University Hospital
- Chang Gung Memorial Hospital, Linkou
- Songklanagarind Hospital, Prince of Songkla University
- Chulalongkorn University
- Ramathibodi Hospital Mahidol University
- Maharaj Nakorn Chiang Mai Chiang Mai University
- Srinagarind Hospital
- Naresuan University
- Nottingham City Hospital
- Royal Marsden Hospital
- The Clatterbridge Cancer Centre NHS Foundation Trust
- Guys Hospital
- The Christie NHS Foundation Trust - PPDS
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Infigratinib (BGJ398) 125 mg
Gemcitabine + Cisplatin
Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.