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