Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00555152
First received: November 6, 2007
Last updated: June 27, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Ductal Breast Carcinoma in Situ
HER2-positive Breast Cancer
Drug: lapatinib ditosylate
Other: placebo
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Reduction in the percent of Ki67 positive cells [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    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.

  • Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria version 3.0 [ Time Frame: Within 5 days prior to surgery ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of ductal carcinoma in situ remaining at resection [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    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: Up to 6 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 60
Study Start Date: January 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lapatinib ditosylate)
Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be premenopausal or postmenopausal
  • Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy
  • The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)
  • All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1
  • If subjects are of reproductive potential, they must agree to use a reliable contraceptive method or be sexually abstinent; subjects must fulfill these conditions beginning at the time of starting study medications and ending one month after study termination
  • Negative serum pregnancy test (beta-human chorionic gonadotropin [HCG]) at baseline (within 30 days of day 0) for women of child bearing potential
  • Serum creatinine =< 1.5 times the institution's upper limit of normal
  • Total bilirubin =< 1.5 times the institution's upper limits of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 times the institution's upper limits of normal
  • Alkaline phosphatase =< 1.5 times the institution's upper limits of normal
  • Albumin =< 1.5 times the institution's upper limits of normal
  • White blood cells (WBC) > 4.0 k/uL
  • Platelet count > 100,000/uL
  • Hematocrit of > 30%
  • Cardiac ejection fraction within normal limits for the institution by multi gated acquisition scan (MUGA) scan or normal cardiac ultrasound (defined as within the upper limit of normal [ULN] for the institution)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Willingness to refrain from donating blood to others during the study

Exclusion Criteria:

  • Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years
  • Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)
  • Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1
  • Individuals currently receiving anticoagulation therapy (e.g., Coumadin) are ineligible
  • Blood urea nitrogen [BUN] > 1.5 x ULN or
  • Creatinine [Cr] > 1.5 x ULN
  • SGOT > 1.5 x ULN
  • Serum glutamate pyruvate transaminase (SGPT) > 1.5 x ULN
  • Alkaline phosphatase > 1.5 x ULN
  • Bilirubin > 1.5x ULN
  • Individuals who are currently participating in a study of an investigational drug
  • Pregnancy, lactation or unwillingness to use a reliable contraceptive method in women of childbearing potential
  • Severe underlying chronic illness or disease, such as uncontrolled diabetes
  • Individuals with known congestive heart disease or previous myocardial infarction are ineligible
  • Patients taking any prohibited medications
  • Individuals with hypokalemia or hypomagnesemia are ineligible unless these conditions are corrected to within normal limits before starting drug
  • Individuals with congenital long QT syndrome or baseline QTcF intervals > 480 msec on electrocardiogram (EKG)
  • Individuals taking anti-arrhythmics, beta blockers, or other medications that may lead to QT prolongation
  • Individuals who have received a cumulative dose of anthracycline therapy greater than 500 mg/m^2 are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555152

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Helen Krontiras    205-934-3028    hkrontir@uabmc.edu   
Principal Investigator: Helen Krontiras         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Powell H. Brown    866-319-4357    NCICTRO@mail.nih.gov   
Principal Investigator: Powell H. Brown         
Sponsors and Collaborators
Investigators
Principal Investigator: Powell Brown M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00555152     History of Changes
Obsolete Identifiers: NCT00570453
Other Study ID Numbers: NCI-2009-00875, NCI-2009-00875, 2008-0086, CDR0000573719, H-19895, P50-CA-58183, P50-CA-58183, P50CA058183, P30CA016672
Study First Received: November 6, 2007
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Ductal, Breast
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Carcinoma, Ductal
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014