Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Infigratinib (BGJ398) 125 mg
Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
  • Drug: BGJ398
    Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
    Other names:
    • Infigratinib
Active Comparator
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.
  • 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.
  • 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.

Recruiting Locations

Banner MD Anderson Cancer Center
Gilbert, Arizona 85234

University of Arizona
Tucson, Arizona 85724

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

St. Joseph Heritage Healthcare
Fullerton, California 92835

USC Norris Cancer Center
Los Angeles, California 90033

University of California Los Angeles
Los Angeles, California 90095

Florida Hospital Medical Group
Orlando, Florida 32804

UF Health Cancer Center at Orlando Health
Orlando, Florida 32806

Northwestern Memorial Hospital
Chicago, Illinois 60611

University Medical Center - New Orleans
New Orleans, Louisiana 70112

Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute
Frederick, Maryland 21702

Massachusetts General Hospital
Boston, Massachusetts 02114

Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center
Detroit, Michigan 48201

Cancer and Hematology Centers of Western Michigan
Grand Rapids, Michigan 49503

William Beaumont Hospital
Royal Oak, Michigan 48073

Atlantic Health System
Summit, New Jersey 07901

NYU Langone Medical Center
New York, New York 10016

Memorial Sloan Kettering Cancer Center
New York, New York 10021

Levine Cancer Institute - Charlotte
Charlotte, North Carolina 28204

University of Cincinnati Medical Center
Cincinnati, Ohio 45267

Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43202

Allegheny Singer Research Institute
Pittsburgh, Pennsylvania 15212

Charleston Oncology
Charleston, South Carolina 29414

Parkland Health and Hospital System
Dallas, Texas 75343

University of Texas Southwestern Medical Center
Dallas, Texas 75390

University of Texas MD Anderson Cancer Center
Houston, Texas 77030

Baylor College of Medicine
Houston, Texas 77096

Hospital Oncologico, Puerto Rico Medical Center
Rio Piedras, Puerto Rico 00935

More Details

NCT ID
NCT03773302
Status
Recruiting
Sponsor
QED Therapeutics, Inc.

Study Contact

QED Therapeutics Clinical Development
877-280-5655
PROOF301.ct@qedtx.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.