Clinical Trials /

Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

NCT03773302

Description:

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 gene fusions/translocations. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.

Related Conditions:
  • Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
  • Official Title: A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial

Clinical Trial IDs

  • ORG STUDY ID: QBGJ398-301
  • SECONDARY ID: 2018-004004-19
  • NCT ID: NCT03773302

Conditions

  • Advanced Cholangiocarcinoma
  • FGFR2 Gene Mutation

Interventions

DrugSynonymsArms
BGJ398InfigratinibInfigratinib (BGJ398) 125 mg
GemcitabineGemcitabine + Cisplatin
CisplatinGemcitabine + Cisplatin

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 gene fusions/translocations. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.

Trial Arms

NameTypeDescriptionInterventions
Infigratinib (BGJ398) 125 mgExperimentalInfigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
  • BGJ398
Gemcitabine + CisplatinActive ComparatorParticipants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.
  • Gemcitabine
  • Cisplatin

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

          -  Documented FGFR2 gene fusions/translocations

          -  Have an archival tissue sample available with sufficient tumor for central FGFR2
             fusion/translocation molecular testing. However, if an archival tissue sample is not
             available, a newly obtained (before randomization) tumor biopsy may be submitted
             instead.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Able to swallow and retain oral medication

          -  Willingness to avoid pregnancy or father children

        Exclusion Criteria:

          -  Received treatment with any systemic anti-cancer therapy for unresectable locally
             advanced or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is
             permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant
             therapy.

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (central imaging assessment)
Time Frame:Approximately 11 months on average
Safety Issue:
Description: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

Measure:Overall survival in participants treated with infigratinib versus gemcitabine with cisplatin
Time Frame:Approximately 15 months on average
Safety Issue:
Description:Defined as time from date of randomization until death due to any cause
Measure:Investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin
Time Frame:Approximately 10 months on average
Safety Issue:
Description:Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
Measure:Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by overall response rate (ORR) determined by blinded independent central assessment and the investigator.
Time Frame:Approximately 10 months on average
Safety Issue:
Description:
Measure:Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by best overall response (BOR) determined by blinded independent central assessment and the investigator.
Time Frame:Approximately 10 months on average
Safety Issue:
Description:
Measure:Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by duration of response (DOR) determined by blinded independent central assessment and the investigator.
Time Frame:Approximately 10 months on average
Safety Issue:
Description:
Measure:Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by disease control rate (PR+CR+SD) determined by blinded independent central assessment and the investigator.
Time Frame:Approximately 10 months on average
Safety Issue:
Description:
Measure:Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability of infigratinib.
Time Frame:Approximately from baseline to last dose date of study treatment + 30 days, approximately 12 months on average
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:QED Therapeutics, Inc.

Trial Keywords

  • cholangiocarcinoma
  • unresectable cholangiocarcinoma
  • metastatic cholangiocarcinoma
  • fibroblast growth factor receptor inhibitor
  • FGFR2
  • FGFR2 gene fusions/translocations
  • BGJ398

Last Updated

December 22, 2020