Clinical Trials /

Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma

NCT02428855

Description:

This research study is studying Dasatinib as a possible treatment for cancer of bile ducts.

Related Conditions:
  • Cholangiocarcinoma
  • Gallbladder Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Phase II Trial of <span class="go-doc-concept go-doc-intervention">Dasatinib</span> in Patients With Isocitrate Dehydrogenase (<span class="go-doc-concept go-doc-biomarker">IDH</span>)-<span class="go-doc-concept go-doc-keyword">Mutant</span> Advanced Intrahepatic Cholangiocarcinoma

Title

  • Brief Title: Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma
  • Official Title: Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma
  • Clinical Trial IDs

    NCT ID: NCT02428855

    ORG ID: 15-007

    Trial Conditions

    Cholangiocarcinoma

    Trial Interventions

    Drug Synonyms Arms
    Dasatinib SPRYCEL Dasatinib

    Trial Purpose

    This research study is studying Dasatinib as a possible treatment for cancer of bile ducts.

    Detailed Description

    This research study is a Phase II clinical trial. Phase II clinical trials test the safety
    and effectiveness of an investigational intervention to learn whether the intervention works
    in treating a specific disease. "Investigational" means that the intervention is being
    studied.

    The standard treatment for metastatic cholangiocarcinoma is combination chemotherapy with
    gemcitabine and cisplatin. The FDA (the U.S. Food and Drug Administration) has not approved
    dasatinib for your specific disease (Cholangiocarcinoma) but it has been approved for other
    uses (Chronic Myeloid Leukemia)

    Trial Arms

    Name Type Description Interventions
    Dasatinib Experimental Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen Dasatinib, oral, daily, predetermined dosage per cycle Radiologic Response Assessment every 2 cycles Dasatinib

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must meet the following criteria on screening examination to be eligible
    to participate in the study:

    - Participants must have unresectable or metastatic histologically confirmed
    intrahepatic cholangiocarcinoma

    - Patients must have either IDH1 or IDH2 mutations (any known mutations) based on the
    SNaPshot platform or other molecular testing platform from either archived tissue or
    fresh biopsy (tested in CLIA-certified lab)

    - Patients with other biliary tract cancers (extrahepatic or gallbladder cancers) with
    IDH1 or IDH2 mutations are allowed

    - Participants must have measurable disease, defined as at least one lesion that can be
    accurately measured in at least one dimension (longest diameter to be recorded) as
    20 mm with conventional techniques or as 10 mm with spiral CT scan. See section 10
    for the evaluation of measureable disease.

    - Participants must have received at least one prior platinum-based regimen for
    advanced cholangiocarcinoma and had progressive disease or become intolerable to the
    regimen

    - Age 18 years.

    - Life expectancy of 3 months.

    - ECOG performance status 0 or 1 (see Appendix A).

    - Participants must have adequate organ and marrow function as defined below:

    - Absolute neutrophil count 1,200/mcL

    - Platelets 75,000/mcL

    - Hemoglobin 9 g/dL

    - Total bilirubin 2.5 x the upper limit of normal

    - AST (SGOT)/ALT (SGPT) 5 X institutional upper limit of normal

    - PT/PTT 1.5 x ULN

    - Creatinine 1.5 or GFR 60 mL/min/1.73m2

    - Serum Albumin 2.8 g/dl

    - Prior chemoembolization, radiofrequency ablation, or radiation to the liver is
    allowed as long as the patient has measurable disease outside of the treated area or
    measurable progression at the site of the treated area

    - Ability to understand and the willingness to sign a written informed consent
    document.

    - Sexually active subjects (men and women) must agree to use medically accepted barrier
    methods of contraception (eg, male or female condom) during the course of the study
    and for 4 months after the last dose of study drug(s), even if oral contraceptives
    are also used. All subjects of reproductive potential must agree to use both a
    barrier method and a second method of birth control during the course of the study
    and for 4 months after the last dose of study drug(s).

    - Women of childbearing potential must have a negative pregnancy test at screening.
    Women of childbearing potential include women who have experienced menarche and who
    have not undergone successful surgical sterilization (hysterectomy, bilateral tubal
    ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is
    defined as amenorrhea 12 consecutive months. Note: women who have been
    amenorrheic for 12 or more months are still considered to be of childbearing
    potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens,
    ovarian suppression or any other reversible reason.

    Exclusion Criteria:

    - Participants who exhibit any of the following conditions at screening will not be
    eligible for admission into the study.

    - Prior treatment with dasatinib

    - Periampullary tumors

    - Chemotherapy, within 4 weeks prior to entering the study (6 weeks for nitrosoureas or
    mitomycin) or those who have not recovered to less than or equal to grade 1 from
    adverse events due to agents administered more than 4 weeks earlier.

    - The subject has received radiation therapy:

    - to bone or brain metastasis within 14 days of the first dose of study treatment

    - to any other site(s) within 28 days of the first dose of study treatment

    - The subject has active brain metastases or epidural disease (Note: Subjects with
    brain metastases previously treated with whole brain radiation or radiosurgery or
    subjects with epidural disease previously treated with radiation or surgery who are
    asymptomatic and do not require steroid treatment for at least 2 weeks before
    starting study treatment are eligible. Neurosurgical resection of brain metastases or
    brain biopsy is permitted if completed at least 3 months before starting study
    treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for
    subjects with known brain metastases is required to confirm eligibility.)

    - The subject has uncontrolled, significant intercurrent or recent illness including,
    but not limited to, the following conditions:

    - Cardiovascular disorders including

    - Congestive heart failure (CHF): New York Heart Association (NYHA) Class III
    (moderate) or Class IV (severe) at the time of screening

    - Concurrent uncontrolled hypertension defined as sustained BP > 140 mm Hg
    systolic, or > 90 mm Hg diastolic despite optimal antihypertensive
    treatment within 7 days of the first dose of study treatment

    - Diagnosed or suspected congenital long QT syndrome

    - Any of the following within 6 months before the first dose of study
    treatment:

    - Unstable angina pectoris

    - Clinically-significant cardiac arrhythmias

    - Stroke (including TIA, or other ischemic event)

    - Myocardial infarction

    - Thromboembolic event requiring therapeutic anticoagulation (Note:
    subjects with a venous filter (e.g. vena cava filter) are not eligible
    for this study)

    - Any history of clinically significant ventricular arrhythmias (such as
    ventricular tachycardia, ventricular fibrillation, or Torsades de
    pointes)

    - Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec),
    may use either the Fridericia and Bazett's correction

    - Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib
    administration

    - Patients should not be taking drugs that are generally accepted to
    have a risk of causing Torsades de Pointes. The following must be
    discontinued at least 7 days prior to starting dasatinib to be
    eligible:quinidine, procainamide, disopyramide, amiodarone, sotalol,
    ibutilide,dofetilide, erythromycins, clarithromycin, chlorpromazine,
    haloperidol, mesoridazine, thioridazine, pimozide, cisapride,
    bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
    halofantrine,levomethadyl, pentamidine, sparfloxacin, lidoflazine

    - Other clinically significant disorders such as:

    - active infection requiring systemic treatment within 28 days before the
    first dose of study treatment

    - serious non-healing wound/ulcer/bone fracture within 28 days before the
    first dose of study treatment

    - Patients with known moderate/severe pleural effusions that are unrelated to
    malignancy or established diagnosis of pulmonary arterial hypertension

    - Concurrent malignancy (other than adequately treated non-melanoma skin cancer,
    superficial transitional cell carcinoma of the bladder, and cervical carcinoma in
    situ) diagnosed within the past 3 years or any currently active malignancy

    - Psychiatric illness/social situations that would limit compliance with study
    requirements.

    - The subject has received any other type of investigational agent within 28 days
    before the first dose of study treatment.

    - The subject is unable to swallow tablets

    - Individuals who are known to be HIV-positive are excluded from this study.

    - Pregnant women are excluded from this study due to the potential for teratogenic or
    abortifacient effects. Because there is an unknown but potential risk of adverse
    events in nursing infants secondary to treatment of the mother with dasatinib,
    breastfeeding should be discontinued if the mother is treated with dasatinib. These
    potential risks may also apply to other agents used in this study.

    - Subjects may not be receiving any other study agents concurrently while on this study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate (ORR)

    Secondary Outcome Measures

    Progression Free Survival (PFS)

    Overall Survival

    Number of Participants with Adverse Events

    Biologic correlative studies of target inhibition

    Trial Keywords

    Cholangiocarcinoma