Clinical Trial: Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer

Brief Summary: 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.

Detailed Summary:

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.

Current Primary Outcome:

• Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS) [ Time Frame: 2-6 weeks from baseline to surgery, up to 6 weeks ]
  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.
• Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0 [ Time Frame: From baseline to 4-5 weeks after surgery ]
  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.

Original Primary Outcome:

• Proliferation, as measured by Ki67 in malignant breast cells
• Toxicity profile at each dose level

Current Secondary Outcome:

• Incidence of Ductal Carcinoma in Situ Remaining at Resection [ Time Frame: 2-6 weeks from baseline to surgery, up to 6 weeks ]
  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.
• Biomarker Analysis of Proliferation Markers [ Time Frame: 2-6 weeks from baseline to surgery, Up to 6 weeks ]
  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.

Original Secondary Outcome:

• Incidence of ductal carcinoma in situ seen at resection
• Biomarker analysis of proliferation markers in normal breast cells and cancerous breast cells

Dates:
Date Received: November 6, 2007
Date Started: January 2008
Date Completion:
Last Updated: October 22, 2015
Last Verified: August 2014