Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer

PRIMARY OBJECTIVES:

I. To assess the clinical complete response rate (CR) after concurrent lapatinib (lapatinib
ditosylate) and radiotherapy in patients with locally advanced or locally recurrent breast
cancer that is refractory to chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the feasibility of assessing breast cancer stem cells (BCSCs) using flow
cytometry and single cell gene expression profiling (SCGEP).

II. To determine the change in the proportion of BCSCs after combined modality therapy.

III. To evaluate the safety and efficacy of the combination of lapatinib and radiotherapy.

IV. To assess the pathologic complete response rate (pCR) in those undergoing surgical
resection.

OUTLINE:

Patients receive lapatinib ditosylate orally (PO) once daily (QD) on day 1 until completion
of radiation therapy. Beginning on day 7, patients undergo radiation therapy for 5-7 weeks.

After completion of study treatment, patients are followed up at 2-4 weeks and then at 6-12
weeks.

Inclusion Criteria:

- Patients with histologically or cytologically confirmed locally advanced breast
cancer that is refractory to chemotherapy or other therapeutic agents or with a
history of breast cancer with new evidence of a local recurrence (defined as a chest
wall or breast recurrence and/or nodal recurrence); the diagnosis will be made based
on clinical and pathologic features

- Patients must be >18 years of age.

- Karnofsky Performance Status (KPS) score > 70

- Patts must have normal organ function as defined below:

- total bilirubin < 1.5 x institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) < 2.5 x institutional upper limit of normal

- creatinine < 1.5 x institutional upper limit of normal

- Patients must have left-ventricular ejection fraction > 50% at baseline.

Exclusion Criteria:

- Patients who have contraindications to radiotherapy, such as scleroderma,
dermatomyositis, or severe cutaneous manifestations of systemic lupus erythematosus
(SLE)

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lapatinib

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, or psychiatric illness/social
situations that would limit compliance with study requirements

- Women who are pregnant or lactating, as well as women of child-bearing potential who
are unwilling or unable to use an acceptable method of birth control to avoid
pregnancy for the duration of the study