Phase II Trial of Capecitabine (Xeloda) and Lapatinib (Tykerb) as First-line Therapy in Patients With HER2/Neu-Overexpressing Advanced or Metastatic Breast Cancer

Inclusion Criteria:

- Histologically confirmed invasive breast cancer

- Stage IIIB, IIIC with T4 lesion or Stage IV disease

- Breast cancer must be determined to be HER2-positive. Assays using fluorescence in
situ hybridization (FISH) require gene amplification and assays using
immunohistochemistry require a strongly positive (3+) staining intensity score in
primary or metastatic tumor tissue

- Measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors)

- Age ³ 18 years of age

- ECOG performance status 0, 1 or 2 (Appendix B)

- Life expectancy of 3 months or longer

- Able to swallow oral medication

- Adequate end organ function

- Left ventricular ejection fraction

- Women of childbearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation

- Written informed consent

Exclusion Criteria:

- Prior treatment with chemotherapy for advanced or metastatic breast cancer

- Prior anti-ErbB1 and/or ErbB2 inhibitor therapy for breast cancer; neoadjuvant or
adjuvant treatment with trastuzumab will be allowed provided the last dose was > 6
months prior to enrollment in study

- Symptomatic or untreated brain metastases or carcinomatous meningitis

- Uncontrolled illnesses including symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia requiring therapy, myocardial infarction within
the past 6 months, or active infection

- History of other primary malignancies in the last 5 years prior to on-study date
except carcinoma in situ of the cervix and nonmelanoma skin cancer

- History of allergic reaction attributed to compounds of similar chemical or biologic
composition to capecitabine and/or lapatinib

- Concurrent treatment with other investigational or commercial anti-cancer agent(s)

- Known dihydropyrimidine dehydrogenase (DPD) deficiency

- Less than 3 weeks since prior radiotherapy

- Less than 2 weeks since prior hormonal therapy

- Known HIV-positive patients receiving combination anti-retroviral therapy are
excluded from the study because of possible pharmacokinetic interactions with
lapatinib

- Pregnant or lactating women at anytime during the study

- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative
colitis)

- Certain medications that act through the CYP450 system are specifically prohibited in
patients receiving lapatinib because in vitro data indicate that the agents has the
potential to interact with cytochrome P450 enzymes CYP3A4. Certain other agents
should be used with caution. Medications that are specifically prohibited can be
found in Appendix C.