A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor
Condition: Advanced Malignant Solid Tumors
MeSH terms: Neoplasms
Intervention: Neratinib; Capecitabine
Intervention description: 240 mg once daily by mouth.; 1500 mg/m^2 twice daily by mouth.
Intervention MeSH terms: Capecitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Neratinib; Capecitabine; Combination; Solid Tumor

Summary:

      This is an open-label, phase 1 study of a single cohort of neratinib (HKI-272) in combination
      with capecitabine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects 20 years and older

          -  Confirmed pathologic diagnosis of a solid tumor not curable with currently available
             therapies, for which neratinib plus capecitabine is a reasonable treatment option.

          -  At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid
             Tumors (RECIST) criteria (Please note: ascites, pleural or pericardial effusion,
             osteoblastic bone metastases, and carcinomatous lymphangitis of the lung will not be
             considered measurable lesions).

          -  Subjects with skin lesions that are measurable by computed tomography (CT) scans or
             magnetic resonance imaging (MRI) as the only site of measurable disease are allowed.

          -  Recovery from all clinically significant adverse events (AEs) related to prior
             therapies (excluding alopecia).

          -  Left ventricular ejection fraction (LVEF) within institutional range of normal as
             measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (not declining
             within 2 weeks before signing the informed consent form [ICF]).

        Screening lab values within the following parameters: Absolute neutrophil count (ANC):
        1.5×109/L (1500/mm3) Platelet count: 100×109/L (100,000/mm3) Hemoglobin: 9.0 g/dL (90 g/L)
        Serum creatinine: 01.5×upper limit of normal (ULN) Total bilirubin: 1.5×ULN (<3 ULN if
        Gilbert's disease) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT):
        2.5×ULN (=5×ULN if liver metastases are present)

          -  For women of childbearing potential, a negative urine or serum pregnancy test result
             before study entry.

          -  All subjects who are biologically capable of having children must agree and commit to
             the use of a reliable method of birth control for the duration of the study and for 28
             days after the last dose of investigational product. A subject is biologically capable
             of having children if he or she is using contraceptives or if his or her sexual
             partner is sterile or using contraceptives.

        Exclusion Criteria:

          -  Prior treatment with anthracyclines with a cumulative dose of doxorubicin >400 mg/m²,
             or of epirubicin >800 mg/m², or the equivalent dose for other anthracyclines or
             derivatives.

          -  Major surgery, chemotherapy, radiotherapy, any investigational agents, or other cancer
             therapy within at least 2 weeks before administration of the first dose of
             investigational product.

          -  Bone as the ONLY site of disease .

          -  Active central nervous system (CNS) metastases, as indicated by clinical symptoms,
             cerebral edema, and/or progressive growth (subjects with a history of CNS metastases
             or cord compression are permitted if they have been definitively treated and are off
             anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1).

        QT (corrected QT (QTc)) interval >0.47seconds or a known history of QTc prolongation or
        torsades de pointes.

          -  Presence of clinically significant or uncontrolled cardiac disease, including
             congestive heart failure (New York Heart Association [NYHA] functional classification
             of 02), angina requiring treatment, myocardial infarction within the past 12 months,
             or any clinically significant supraventricular arrhythmia or ventricular arrhythmia
             requiring treatment or intervention.

          -  Pregnant or breastfeeding women.

          -  Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major
             symptom (eg, Crohn's disease, malabsorption, or grade 2 or higher diarrhea of any
             etiology at baseline).

          -  Inability or unwillingness to swallow tablets (neratinib and capecitabine).

          -  Subjects with active or uncontrolled renal insufficiency, in whom medication dose
             adjustments are indicated.

          -  Subject known to be human immunodeficiency virus (HIV) seropositive and/or have acute
             or chronic hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) or
             hepatitis C infection (anti-HCV positive).

          -  Known history of hypersensitivity to capecitabine or any of it components, including
             5-FU.

          -  Any other cancer within 5 years prior to screening with the exception of contralateral
             breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated
             basal or squamous cell carcinoma of the skin.

          -  Clinically significant ongoing or recent infection within 2 weeks before
             administration of the first dose of investigational product.

          -  Evidence of significant medical illness or abnormal laboratory findings that in the
             investigator's judgment will substantially increase the risk associated with the
             subject's participation in and completion of the study, or preclude the evaluation of
             the subject's response. Examples include, but are not limited to, serious active
             infection, (ie, requiring intravenous antibiotic or antiviral agent) or uncontrolled
             major seizure disorder, significant pulmonary disorder (eg, interstitial pneumonitis,
             pulmonary hypertension), or psychiatric disorder that would interfere with subject
             safety or informed consent.