Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer
Condition: Relapsed Breast Cancer; Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Capecitabine; Docetaxel; nab-Paclitaxel
Intervention description: Small molecule tyrosine kinase inhibitor; Chemotherapy; Chemotherapy; Chemotherapy
Intervention MeSH terms: Paclitaxel; Docetaxel; Capecitabine; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ErbB1; ErbB2; GW572016; lapatinib; Relapsed breast cancer; dual tyrosine kinase inhibitor; MBC; EGFR; Her-2/neu; FISH amplification

Summary:

      This study will evaluate the safety and efficacy of lapatinib in combination with
      chemotherapy (capecitabine, docetaxel, nab-paclitaxel) in subjects with ErbB2-overexpressing
      breast cancer whose disease has progressed during or within 12 months after completion of
      trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent.

          -  Histologically/cytologically confirmed breast cancer;

        If the disease is restricted to a solitary lesion, the neoplastic nature of the lesion must
        be confirmed by cytology or histology.

          -  Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid
             Tumors) [Therasse, 2000].

          -  Documented amplification of the ErbB2 gene by fluorescence in situ hybridization
             (FISH) or documented overexpression of the ErbB2 protein by 3+ IHC in primary or
             metastatic tumor tissue.

          -  Subjects must have relapsed breast cancer where the disease progressed during or ≤ 12
             months after completion of trastuzumab-containing therapy in the neoadjuvant or
             adjuvant setting.

        Note: Progression is defined using RECIST criteria, that is, either the appearance of new
        lesions or a >=20% increase in the sum of longest diameter (LD).

          -  Subjects must not have received prior anti-cancer therapy for metastatic breast cancer
             (MBC). Subjects who received prior antihormonal agents combined with trastuzumab for
             the treatment of disease which first presented as ER positive MBC and recurred while
             receiving trastuzumab or ≤ 3 months after completing this therapy are eligible.

          -  Subjects with stable central nervous system (CNS) metastases as confirmed by
             computerized tomography (CT)/magnetic resonance imaging (MRI) are allowed. Treatment
             with prophylactic anticonvulsants is permitted, unless listed within the Prohibited
             Medications.

          -  Subjects must have a baseline cardiac ejection fraction (LVEF) ³50% measured by
             echocardiogram (ECHO) (or multigated acquisition (MUGA) scan if an ECHO cannot be
             performed). The same modality used at baseline must be used for repeat assessment
             throughout study. Only subjects with controlled or asymptomatic angina or arrhythmias
             are eligible.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.

          -  Subjects must have archived tumor tissue from the initial diagnosis available for
             analysis. If tissue from the initial diagnosis is not available, then tissue must be
             obtained from a recurrent or metastatic site prior to initiating study treatment.

          -  Female ≥18 years.

          -  Subject must have adequate organ function as defined in Table 1.

          -  Table 1: Baseline Laboratory Values for Adequate Organ Function.

        SYSTEM

        Hematologic:

        Absolute neutrophil count: ≥1.5 X 10^9/L

        Hemoglobin: ≥9 g/dL

        Platelets: ≥ 75 X 10^9/L

        Hepatic:

        AST, ALT and Alkaline phosphatase: ≤ 2.5 X ULN

        Unless concomitant docetaxel, then ≤ 1.5 x ULN for AST and ALT, with AP ≤ 2.5 x ULN

        Unless documented liver metastasis, then ≤ 5 x ULN

        Serum bilirubin: ≤ 2.0 X ULN

        Albumin: ≥ 2.5 g/dL

        Renal:

        Serum Creatinine: ≤ 1.5 mg/dL

          -  OR - Calculate Creatinine Clearance: ≥ 40 mL/min

               1. Calculated by the Cockcroft and Gault Method [Cockcroft , 1976].

        Exclusion Criteria:

          -  Pregnant or lactating females.

          -  Women of childbearing potential who do not practice approved contraceptive methods
             (for example, intrauterine device [IUD], birth control pills, or barrier device)
             beginning 2 weeks before the first dose of investigational product and for 28 days
             after the final dose of investigational product.

          -  History of other malignancy. However, subjects who have been disease-free for 5 years,
             or subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible.

          -  Concurrent therapy given to treat cancer (chemotherapy, radiation therapy,
             immunotherapy, biologic therapy, anti-hormonal therapy) while taking study medication.

          -  Unresolved or unstable, serious toxicity from prior administration of another
             investigational drug and/or of prior cancer treatment.

          -  Malabsorption syndrome or resection of the stomach or small bowel significantly
             affecting gastrointestinal function.

          -  Have current active haptic or biliary disease (with excpetion of patients with
             Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
             disease per investigator assessment).

          -  Concurrent disease or condition that, in the opinion of the physician, would make the
             subject inappropriate for study participation or any serious medical disorder that
             would interfere with the subject's safety (for example, uncontrolled infection, or any
             psychiatric condition prohibiting understanding or rendering of informed consent).

          -  Concurrent treatment with an investigational agent or participation in another
             clinical trial involving investigational agents for anti-cancer therapy.

          -  Bisphosphonates may not be initiated after the first dose of study medication.

          -  Considered by the Investigator to have a life expectancy less than 3 months.

          -  Not able to swallow or retain oral medication.

          -  The subject with a known unmanageable hypersensitivity reaction or idiosyncrasy to
             drugs chemically related to lapatinib or excipients and those related to capecitabine,
             docetaxel, nab paclitaxel or their excipients.