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

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Trial ID:
IRB-19-7395
Darren Sigal
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.

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

Contact Info:

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

Why isn't this trial accepting new patients?

The trial may have a limited enrollment number, reached its maximum, or come to the end of its enrollment period. View trials that are recruiting

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