Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer
Condition: Metastases, Brain
MeSH terms: Breast Neoplasms; Neoplasm Metastasis
Intervention: capecitabine; lapatinib; trastuzumab
Intervention description: oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle; oral medication; daily dose taken once a day; infusion therapy; loading dose of 8mg/kg, followed by 6mg/kg given every 3 weeks
Intervention MeSH terms: Capecitabine; Trastuzumab; Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 540.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ErbB2; HERCEPTIN; XELODA; ErbB1; TYKERB; metastatic breast cancer; trastuzumab; breast cancer; capecitabine; lapatinib; brain metastases; HER2 positive; TYVERB

Summary:

      This open label study was designed to evaluate Lapatinib effect on incidence of brain
      metastases in ErbB2 (HER2) positive metastatic breast cancer patients exposed to prior
      taxanes or anthracyclines.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females at least 18 years old;

          -  ECOG Performance Status 0-2;

          -  Histologically or cytologically confirmed HER2-positive invasive breast cancer, with
             Stage IV disease;

          -  Prior treatment with taxanes or anthracyclines is required;

          -  Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and
             radiation therapy is permitted;

          -  Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal;

          -  Concurrent treatment with bisphosphonates is permitted, however treatment must be
             initiated prior to the first dose of study therapy;

          -  Able to swallow and retain oral medications;

          -  Women with potential to have children must be willing to practice acceptable methods
             of birth control during the study;

          -  Normal organ and marrow function.

        Exclusion Criteria:

          -  History and/or current evidence of CNS metastases. Baseline MRI scan by Independent
             Reviewer to confirm no brain mets;

          -  Concurrent treatment with an investigational agent or participation in another
             treatment clinical trial;

          -  Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including
             but not limited to trastuzumab-DM1 and neratinib) and capecitabine;

          -  Known DPD deficiency;

          -  Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or
             hormonal therapy for treatment of cancer;

          -  History of allergic reactions attributed to compounds chemically related to lapatinib
             (quinazolines), capecitabine, fluorouracil or any excipients;

          -  Concomitant use of CYP3A4 inhibitors or inducers;

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel;

          -  History of immediate or delayed hypersensitivity reaction to gadolinium contrast
             agents, or other contraindication to gadolinium contrast and other known
             contraindication to MRI;

          -  Concurrent disease or condition that would make the subject inappropriate for study
             participation or any serious medical or psychiatric disorder that would interfere with
             the patient's safety or compliance to study procedures;

          -  have acute or currently active/requiring anti-viral therapy hepatic or biliary disease
             (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver
             metastases or stable chronic liver disease);

          -  Any on-going toxicity from prior anti cancer therapy except alopecia;

          -  Active cardiac disease;

          -  Uncontrolled infection;

          -  History of other malignancy, unless curatively treated with no evidence of disease for
             at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated
             non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are
             eligible;

          -  Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of protocol treatment;

          -  Pregnant or lactating females.