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Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

Primary Purpose

Ductal Breast Carcinoma In Situ, HER2/Neu Positive

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Lapatinib Ditosylate
Placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ductal Breast Carcinoma In Situ

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (lapatinib ditosylate)

Arm II (placebo)

Arm Description

Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.

Patients receive placebo PO QD for 2-6 weeks until the time of surgery.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
November 6, 2007
Last Updated
March 21, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00555152
Brief Title
Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ
Official Title
Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
August 19, 2009 (Actual)
Primary Completion Date
August 28, 2014 (Actual)
Study Completion Date
August 28, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ductal Breast Carcinoma In Situ, HER2/Neu Positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (lapatinib ditosylate)
Arm Type
Experimental
Arm Description
Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Lapatinib Ditosylate
Other Intervention Name(s)
Tykerb
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Description
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
Title
Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Description
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
Secondary Outcome Measure Information:
Title
Incidence of Ductal Carcinoma in Situ Remaining at Resection
Description
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
Title
Biomarker Analysis of Proliferation Markers
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Powel Brown
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

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