Lapatinib for Treatment of Ductal Carcinoma In Situ (DCIS) of the Breast - Full Text View

Sponsors and Collaborators:	Indiana University GlaxoSmithKline
Information provided by:	Indiana University
ClinicalTrials.gov Identifier:	NCT00857714

Purpose

The purpose of this study is to establish the utility of lapatinib in the treatment of DCIS, particularly ER-negative DCIS.

Condition	Intervention
Ductal Carcinoma In Situ	Drug: lapatinib

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Official Title:	Lapatinib in the Treatment of Ductal Carcinoma in Situ of the Breast

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

Drug Information available for: Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Further study details as provided by Indiana University:

Primary Outcome Measures:

To identify gene signature that denotes effect of lapatinib therapy in breast cancer cell lines. To assess effect of lapatinib therapy in patients with ductal carinoma in situ of the breast using the gene signature developed as a surrogate marker. [ Time Frame: Two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess toxicity associated with short therapy with lapatinib. [ Time Frame: Two years. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	August 2009
Estimated Study Completion Date:	December 2019
Estimated Primary Completion Date:	December 2019 (Final data collection date for primary outcome measure)

Intervention Details:

1500 mg lapatinib for 14-21 days

Detailed Description:

Ductal carcinoma in situ (DCIS) of the breast is a pre-malignant lesion of the breast, which is associated with a marked increase in the likelihood of developing invasive breast cancer. Since DCIS tends to be associated with microcalcifications, it is detected with an increased frequency in patients being screened with mammographic techniques. The treatment of DCIS is based on a number of parameters; local treatment depends on the size of the lesion, grade and margins. The only systemic treatment currently available is in the form of endocrine therapy; it depends on the expression of estrogen receptor (ER). Randomized trials have shown that the treatment of DCIS with breast conserving therapy and radiation is as effective as simple mastectomy.

The efficacy of tamoxifen in reducing the incidence of further invasive or non-invasive breast cancer has been established. In addition to surgery (with or without radiation), patients with ER positive disease also receive anti-estrogen therapy. Current guidelines do not recommend any additional therapy for ER-negative DCIS.

The rationale for the proposed study is based on the observations that HER2 is expressed at high levels in higher grades of DCIS, which typically lack ER. In addition, an inverse relationship between ER expression and the expression of EGFR has also been demonstrated. Lapatinib is active against both these receptors and may have therapeutic action in ER negative DCIS.

We propose to treat the patients with drug in the interval between biopsy diagnosis and definitive surgery.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age greater than or equal to 18 years.
Patients with operable, biopsy-proven DCIS detected by screening mammography.
ER/PR negative DCIS.
DCIS that is positive for HER-2 &/or EGFR, which is defined as IHC 3+.
Women of childbearing potential willing to use an accepted and effective barrier method of contraception.
ECOG performance status ≤2
Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram.
Ability to understand and the willingness to sign a written informed consent document.
Patients must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/microL
- absolute neutrophil count ≥1,500/microL
- platelets ≥100,000/microL
- total bilirubin within normal institutional limits
- AST (SGOT)/ALT(SGPT) within normal institutional limits
- creatinine within normal institutional limits OR creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (using Cockcroft-Gault formula)

Exclusion Criteria:

Invasive breast cancer
ER+ or PR+ DCIS
Pregnant or breast feeding women
Patients who have had prior treatment with EGFR targeting therapies.
Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy.

In addition, all herbal (alternative) medicines are excluded one week before starting lapatinib and for the duration of lapatinib therapy.
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib.
Have ANY hepatic or biliary disease or dysfunction.
Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
ANY history of cardiac disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857714

Contacts

Contact: Sarah A. Dutkevitch, RN

317-274-5459

sdutkevi@iupui.edu

Locations

United States, Indiana
Indiana University	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Sarah A. Dutkevitch, RN 317-264-6748 sdutkevi@iupui.edu
Principal Investigator: Sunil Badve, MD
Sub-Investigator: Erika Rager, MD

Sponsors and Collaborators

Indiana University

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Indiana University ( Sunil Badve, MBBS )
Study ID Numbers:	0812-11
Study First Received:	March 6, 2009
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00857714 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Indiana University:

DCIS
breast

Study placed in the following topic categories:

Carcinoma, Ductal
Skin Diseases
Carcinoma in Situ
Breast Neoplasms
Lapatinib
Carcinoma, Ductal, Breast

Carcinoma, Intraductal, Noninfiltrating
Adenocarcinoma
Protein Kinase Inhibitors
Breast Diseases
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Breast Neoplasms
Enzyme Inhibitors
Lapatinib
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma
Carcinoma, Ductal

Neoplasms
Neoplasms by Site
Therapeutic Uses
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Neoplasms, Ductal, Lobular, and Medullary
Adenocarcinoma
Breast Diseases
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 10, 2009