Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions
Condition: Malignant Hepatobiliary Neoplasm
Intervention: Laboratory Biomarker Analysis; Ponatinib Hydrochloride; Quality-of-Life Assessment
Intervention description: Correlative studies; Given PO; Ancillary studies
Intervention MeSH terms: Ponatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot phase II trial studies how well ponatinib hydrochloride works in treating patients
      with biliary cancer that has spread to other places in the body and that have alterations
      (fusions) in a gene known as fibroblast growth factor receptor 2 (FGFR2). Ponatinib
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological/cytological confirmation of biliary cancer

          -  Confirmation of advanced biliary cancer that is refractory or intolerant to
             gemcitabine or fluoropyrimidine based therapy with FGFR2 fusion [using next-gen
             sequencing assays (such as Foundation One) or fluorescent in situ hybridization (FISH)
             break-apart assays] or FGFR pathway mutation/amplification [using next-gen sequencing
             assays (such as Foundation One)]; assays must be performed in a Clinical Laboratory
             Improvement Amendments [CLIA] certified laboratory and done as a CLIA validated test
             or research use only [RUO] in a CLIA laboratory

          -  Measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome

          -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) < 3 x ULN

          -  Creatinine =< 1.5 x ULN

          -  Serum lipase and amylase =< 2.5 x ULN; NOTE: if subject has tumor involvement in the
             liver =< 3 x ULN

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Recovered from prior radiotherapy and/or systemic therapy related toxicities to grade
             =< 1

          -  Provide informed written consent

          -  Life expectancy >= 3 months

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study); Note: during the Active Monitoring Phase of a study (i.e., active
             treatment and observation), participants must be willing to return to the consenting
             institution for follow-up

          -  Female and male patients who are fertile agree to use an effective form of
             contraception with their sexual partners from registration through 4 months after the
             end of treatment

          -  Ability to complete questionnaire(s) by themselves or with assistance

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy; NOTE: patients with a known
             history of HIV infection are not eligible for this trial

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Prior systemic chemotherapy, radiation therapy or major surgery =< 30 days prior to
             registration

          -  Concurrent use of any other approved or investigational anticancer agents, including
             hormonal agents

          -  Prior nitrosourea or mitomycin C =< 6 weeks prior to registration

          -  Patients with gastrointestinal comorbidities that would affect intake or absorption of
             ponatinib

          -  Untreated or progressive brain metastases

          -  Prior treatment with or allergic reactions attributed to compounds of similar chemical
             or biologic composition to ponatinib

          -  Clinically uncontrolled hypertension (diastolic blood pressure > 90 mm mercury [Hg];
             systolic > 140 mm Hg); Note: patients with hypertension should be undergoing treatment
             at study entry for blood pressure control

          -  Previous or concurrent malignancy except adequately treated basal or squamous cell
             skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively
             and without evidence of recurrence for at least 5 years

          -  History of significant bleeding disorder unrelated to cancer

          -  History of acute pancreatitis within 1 year prior to registration, chronic
             pancreatitis, alcohol abuse or uncontrolled hypertriglyceridemia (triglycerides > 450
             mg/dL)

          -  Clinically significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not restricted to:

               -  Any history of myocardial infarction, stroke, or revascularization

               -  Unstable angina or transient ischemic attack within 6 months prior to
                  registration

               -  Congestive heart failure within 6 months prior to registration, or left
                  ventricular ejection fraction (LVEF) less than lower limit of normal per local
                  institutional standards within 6 months prior to registration

               -  History of clinically significant (as determined by the treating physician)
                  atrial arrhythmia

               -  Any history of ventricular arrhythmia

               -  Active venous thromboembolism including deep venous thrombosis or pulmonary
                  embolism that is not amenable to treatment with anticoagulants

               -  Patients with congenital prolonged QT syndromes and abnormal baseline prolonged
                  corrected QT (QTc) (> 450 ms in men and > 470 ms in women)

               -  Patients with an ejection fraction =< 50% as assessed by a baseline
                  echocardiogram

          -  Taking medications that are known to be associated with torsades de pointes

          -  Taking any medications or herbal supplements that are known to be strong inhibitors of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) =< 14 days prior to
             registration