This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo. II. Determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib at 1000 mg as compared to women taking placebo. SECONDARY OBJECTIVES: I. Determine whether lapatinib treatment affects the incidence of DCIS seen at the time of surgical excision. II. Determine whether treatment with lapatinib will modulate breast tissue histology or the expression of specific biomarkers in normal and DCIS breast cancer cells. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) for 2-6 weeks until the time of surgery. ARM II: Patients receive placebo PO QD for 2-6 weeks until the time of surgery. After completion of study treatment, patients are followed for 4-5 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
22
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
M D Anderson Cancer Center
Houston, Texas, United States
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.
Time frame: 2-6 weeks from baseline to surgery, up to 6 weeks
Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.
Time frame: From baseline to 4-5 weeks after surgery
Incidence of Ductal Carcinoma in Situ Remaining at Resection
Number of participants with DCIS incidence on surgical excision. Differences in histologic response (disappearance of DCIS) will be evaluated using Fisher's exact test. Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Time frame: 2-6 weeks from baseline to surgery, up to 6 weeks
Biomarker Analysis of Proliferation Markers
Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Time frame: 2-6 weeks from baseline to surgery, Up to 6 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.