Clinical Trials /

Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions

NCT02265341

Description:

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.

Related Conditions:
  • Cholangiocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ponatinib Hydrochloride</span> in Treating Patients With Advanced Biliary Cancer With <span class="go-doc-concept go-doc-biomarker">FGFR2</span> Fusions

Title

  • Brief Title: Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions
  • Official Title: Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions
  • Clinical Trial IDs

    NCT ID: NCT02265341

    ORG ID: MC1345

    NCI ID: NCI-2014-02075

    Trial Conditions

    Malignant Hepatobiliary Neoplasm

    Trial Interventions

    Drug Synonyms Arms
    Ponatinib Hydrochloride AP24534, AP24534 HCl, Iclusig, multitargeted tyrosine kinase inhibitor AP24534 Treatment (ponatinib hydrochloride)

    Trial Purpose

    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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To assess the clinical benefit rate (confirmed complete or partial response or stable
    disease for 4 or more cycles) of ponatinib (ponatinib hydrochloride) in fibroblast growth
    factor receptor (FGFR) aberrant advanced biliary cancers.

    SECONDARY OBJECTIVES:

    I. To estimate progression free survival, overall survival, and cancer antigen 19-9 (CA19-9)
    response rate of these patients.

    II. To estimate the adverse event profile of ponatinib.

    TERTIARY OBJECTIVES:

    I. Establish preliminary correlations between FGFR2 fusions and evidence of any clinical
    benefit.

    II. Assess preliminary evaluation of FGFR2 pathway perturbation with ponatinib. III. To
    describe patient-reported health-related quality of life and symptoms.

    OUTLINE:

    Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
    repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 6 months.

    Trial Arms

    Name Type Description Interventions
    Treatment (ponatinib hydrochloride) Experimental Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ponatinib Hydrochloride

    Eligibility Criteria

    Inclusion Criteria:

    - Histological/cytological confirmation of biliary cancer

    - Confirmation of advanced biliary cancer with FGFR2 fusion detected using next-gen
    sequencing assays (such as Foundation One) or fluorescent in situ hybridization
    (FISH) break-apart assays (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) refractory or intolerant to
    gemcitabine or fluoropyrimidine based therapy

    - 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Clinical benefit rate, which includes confirmed tumor response (complete response [CR] or partial response [PR]) or stable disease (SD)

    Secondary Outcome Measures

    Progression-free survival

    Survival time

    Change in CA 19-9 response, defined to be a >= 50% reduction from baseline

    Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Trial Keywords