ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

Inclusion criteria:

* Histologically confirmed invasive breast cancer with stage IV disease
* If trastuzumab was administered in the adjuvant setting, \>12 months must have elapsed since discontinuation of trastuzumab therapy
* If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred ≥12 months after completion of this treatment
* Had tumors that overexpress ErbB2 defined as either: 3+ by IHC OR c-erbB2 gene amplification by FISH OR 0, 1+, 2+ by IHC and c-erbB2 gene amplification by FISH.
* Patients must have tumor tissue available for central testing, and must have Measurable lesion(s) according to RECIST
* Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception
* Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication
* Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
* For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy;
* Able to swallow and retain oral medication
* Cardiac ejection fraction within institutional range of normal
* Patient must have adequate organ function

Exclusion criteria:

* Pregnant or lactating females;
* Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization;
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Patients with ulcerative colitis are also excluded;
* History of other malignancy; however, patients who have been disease-free for five years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
* Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety;
* Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
* Peripheral neuropathy of Grade 2 or greater;
* Active or uncontrolled infection;
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
* Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure;
* Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
* Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy);
* Concurrent treatment with an investigational agent or participation in another clinical trial;
* Concurrent treatment with any medication on the prohibited medications list.
* Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment.
* Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting;
* A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients;
* A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients;
* A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients;
* Non compliance with any of the screening procedures