Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Advanced Or Metastatic Breast Cancer

Inclusion Criteria

• A subject will be eligible for inclusion in this study only if all of the following criteria apply:
• Women ≥ 18 years of age with a life expectancy of ≥ 12 weeks.
• Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Histologically confirmed invasive breast cancer with incurable stage IIIb, stage IIIc with T4 lesion, or stage IV disease at primary diagnosis or at relapse after curative-intent surgery.
• No prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic or recurrent disease (other than neoadjuvant or adjuvant therapy). Prior hormonal therapy (e.g., tamoxifen, raloxifen or an aromatase inhibitor) for advanced or metastatic disease is permitted provided at least 2 weeks have elapsed between the completion of the prior therapy and start of study drugs.
• Note: Subjects must have documented progressive disease (PD) or be intolerant to hormonal therapy. This must be documented in the source documentation.
• Prior neoadjuvant therapy and/or adjuvant therapy is permitted.
• Note:
• (a) Subjects who have received both neoadjuvant and adjuvant therapies must have at least 6 months between completion of the chemotherapy-component of adjuvant therapy and start of study drug(s)
• (b) Subjects who have received only adjuvant therapy must have at least 6 months between completion of the chemotherapy-component of adjuvant therapy and start of study drug(s)
• (c) Subjects who have received only neoadjuvant therapy must have at least 6 months between completion of neoadjuvant therapy and start of study drug(s)
• (d) Subjects who have received trastuzumab or hormonal agents as all or part of adjuvant therapy are eligible provided: (1) 2 weeks have elapsed since last dose (2) 6 months have elapsed between the start of trastuzumab or hormonal therapy and start of study drugs.
• Radiotherapy prior to initiation of randomized therapy to a limited area (e.g., palliative treatment for painful disease) other than the sole site of measurable and assessable disease is allowed however, subjects must have completed treatment at least 4 weeks prior to starting study drugs, and must have recovered from all treatment-related toxicities prior to starting pazopanib and/or lapatinib.
• Documented amplification of ErbB2 by Fluorescence In Situ Hybridization (FISH) in either the primary or metastatic tumor tissue. Archived tumor tissue must be provided for ErbB2 FISH testing by the central laboratory, which will be used to determine eligibility.
• Note: Subjects that have documented ErbB2 amplification based on prior FISH testing or documented ErbB2 overexpression based on prior immunohistochemistry (IHC) with a value of 3+ are eligible, however, archived tumor tissue must be provided for confirmation by the central laboratory. If the results from prior testing are not confirmed by the central laboratory, then the subject can continue to receive study drug(s) at the discretion of the investigator, but will be excluded from the statistical analysis.
• Archived tumor tissue (paraffin-embedded) must be available to correlate tumor response with intra-tumoral genetic changes as well as expression levels of relevant biomarkers. Results of biomarkers will not be used to determine subject eligibility for the study.
• Ability to swallow and retain oral medication.
• Disease must be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST).
• Subjects must have chosen treatment with lapatinib and/or pazopanib as initial treatment over other initial treatments (such as cytotoxic chemotherapy regimens or trastuzumab as a single agent) for locally advanced or metastatic disease.
• Adequate organ function as defined below:
• System (Laboratory Values)
• Hematologic: Absolute neutrophil count (ANC) (≥1.5 X 10