Lapatinib in Combination With Vinorelbine
Condition: Cancer
Intervention: lapatinib and Vinorelbine
Intervention description: Patients will receive 1250mg lapatinib once a day and vinorelbine 25mg/sqm IV Day 1and Day 8, every 3 week for 24 weeks.
Intervention MeSH terms: Vinorelbine; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lapatinib; breast cancer

Summary:

      This is a Multicenter, Open-Label, Phase II Study of lapatinib in Combination with
      Vinorelbine in women with documented evidence of HER2/neu positive breast cancer which is
      metastatic or recurrent and with or without prior chemotherapy or anti-HER2/neu targeted
      therapy in the metastatic and relaps setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the breast.

          -  Patients must be > 18 years of age

          -  Metastatic breast cancer (stage IV) at primary diagnosis or at relapse after curative
             intent therapy.

          -  Laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive
             component of the primary or metastatic lesion

          -  Patients must have evidence of metastatic disease, but measurable disease is not
             mandatory.

          -  The patients may have received or not prior treatment with chemotherapeutic agents
             including taxanes, trastuzumab or anthracycline in the adjuvant or metastatic setting
             is permitted.

          -  Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are
             permitted provided that at least 4 weeks have elapsed since the last fraction of
             radiation therapy and all treatment related adverse events are < grade 1 at the time
             of enrollment.

          -  Prior radiation to a solitary metastatic lesion is permitted provided that progression
             post radiation has been documented.

          -  Patients must have life expectancy > 3 months.

          -  ECOG performance status 0, 1 or 2 (see Appendix II).

          -  Patients must have normal organ and marrow function measured within 14 days prior to
             enrollment as defined Table 1.

          -  Left ventricular ejection fraction > 50% as demonstrated by MUGA scan/echocardiogram
             within 4 weeks prior to enrollment.

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to
             enrollment and must use an acceptable method of contraception for the duration of the
             study.

        Female patients who are lactating should discontinue nursing prior to the first dose of
        investigational product and should refrain from nursing throughout the treatment period and
        for 14 days following the last dose of investigational product.

          -  The patient must sign the consent form prior to enrollment.

          -  Patients must be accessible for treatment and follow-up.

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except: adequately treated DCIS,
             adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the
             cervix, or other solid tumours (non-breast) curatively treated with no evidence of
             disease for > 5 years.

          -  Patients receiving ongoing anticancer treatment or other investigational anti-cancer
             agents for breast cancer or patients who have used an investigational drug within 30
             days or 5 half-lives (if known), whichever is longer, preceding the date of
             enrollment.

          -  Patients with symptomatic CNS metastases (including leptomeningeal involvement).

          -  Patients with only bone metastasis.

          -  Patients with serious cardiac illness or condition including, but not limited to:

        history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF<50%)
        high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block,
        supraventricular arrhythmias which are not adequately rate-controlled) unstable angina
        pectoris requiring anti-anginal medication clinically significant valvular heart disease
        evidence of transmural infarction on ECG inadequately controlled hypertension (systolic
        blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg).

        New York Heart Association (NYHA) Class III or IV functional status (see Appendix X)

          -  Patients who have received vinorelbine as a prior therapy in the metastatic and
             recurrent setting.

          -  Patients with serious illness or medical condition which would not permit the patient
             to be managed according to the protocol including, but not limited to:

          -  History of significant neurologic or psychiatric disorder which would impair the
             ability to obtain consent or limit compliance with study requirements.

          -  Active uncontrolled infection. Serious or non-healing wound, ulcer, or bone fracture.

          -  Patients with GI tract disease resulting in an inability to take oral medication such
             as but not limited to malabsorption syndrome, a requirement for IV alimentation, prior
             surgical procedures affecting absorption (for example resection of stomach or small
             bowel) or uncontrolled inflammatory GI disease (e.g. Crohn's, ulcerative colitis).

          -  Patients receiving CYP3A4 inhibitors or inducers are not eligible unless it has been >
             7 and > 14 days, respectively since the last dose of medication before the start of
             protocol treatment (see Appendix IX). For amiodarone in particular, dosing is
             prohibited for at least 6 months prior to the start of protocol treatment.

          -  Patients with history of allergic or hypersensitivity reactions to any study drug or
             their excipients or with a history of allergic reactions attributed to compounds with
             similar chemical composition to any of the study drugs.

          -  Pregnant or lactation women