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 (Immunohistochemistry 3+ or Fluorescent in-situ hybridisation gene amplification)
• Patients must have tumor tissue available for central testing Measurable lesion(s)
• 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