Phase I/II Study of Lapatinib in Combination With Paclitaxel as 1L Chemotherapy for ErbB2-positive MBC

Inclusion Criteria:

* Prior written consent in participating in the study by the subject or his/her private attorney.
* Japanese female \>=18 years of age.
* Invasive breast cancer with stage IV disease.
* Documentation by local laboratory of ErbB2 status by immunohistochemistry (IHC) or amplification by fluorescence in situ hybridization (FISH).
* If a taxane had been administered in the neoadjuvant or adjuvant setting, progression must have occurred \>12 months after completion of this treatment and the patients recovered from all associated toxicities.
* Measurable lesion(s) according to RECIST criteria.
* Radiotherapy as palliative treatment for painful metastatic disease is permitted but must have been stopped within 2 weeks prior to initiation of any investigational treatment.
* For those patients whose disease is ER+ and/or PR+ one of the following criteria should be met:

  * Patient with visceral disease that requires chemotherapy (e.g., patients with liver or lung metastases).
  * Rapidly progressing or life threatening disease that are considered to be inapplicable to hormonal therapy, as determined by the investigator.
  * Patients who received hormonal therapy and are no longer benefiting from this therapy and the hormonal treatment must have been stopped before the first dose of investigational treatment.
  * Subjects recovered from all the associated toxicities by prior endocrine therapy.
* Eastern cooperative oncology group (ECOG) Performance status (PS) of 0 or 1.
* Able to swallow and retain oral medication.
* Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scan is accepted in cases where an echocardiogram cannot be performed or is inconclusive.
* Adequate organ function.

Exclusion Criteria:

* Pregnant or lactating females at anytime during the study.
* Received prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic disease.
* History of other malignancy.
* Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab, in the adjuvant setting.
* Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment.
* Used an investigational drug within 30 days or five half-lives, whichever is longer, preceding the first dose of investigational treatment.
* Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior anti-cancer treatment.
* Uncontrolled infection.
* Patients having at least positive antibody either to HBs or HBc.
* Patients who have had a positive HCV antibody.
* Peripheral neuropathy grade 2 or greater.
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
* Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.
* Known history or concurrent condition of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
* Concurrent treatment with prohibited medications.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel or lapatinib or their excipients.
* Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).