Lapatinib for Treatment of Ductal Carcinoma In Situ (DCIS) of the Breast

This study has been terminated.
(Terminated due to low accrual)
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00857714
First received: March 6, 2009
Last updated: April 1, 2013
Last verified: April 2013
  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: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Lapatinib in the Treatment of Ductal Carcinoma in Situ of the Breast

Resource links provided by NLM:


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 ]

Enrollment: 1
Study Start Date: April 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: lapatinib
    1500 mg lapatinib for 14-21 days
    Other Name: Tykerb
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:

  1. Age greater than or equal to 18 years.
  2. Patients with operable, biopsy-proven DCIS detected by screening mammography.
  3. ER/PR negative DCIS.
  4. DCIS that is positive for HER-2 &/or EGFR, which is defined as IHC 3+.
  5. Women of childbearing potential willing to use an accepted and effective barrier method of contraception.
  6. ECOG performance status ≤2
  7. Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram.
  8. Ability to understand and the willingness to sign a written informed consent document.
  9. 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:

  1. Invasive breast cancer
  2. ER+ or PR+ DCIS
  3. Pregnant or breast feeding women
  4. Patients who have had prior treatment with EGFR targeting therapies.
  5. 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.
  6. 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.
  7. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib.
  8. Have ANY hepatic or biliary disease or dysfunction.
  9. 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).
  10. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
  11. ANY history of cardiac disease.
  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: NCT00857714

Locations
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
GlaxoSmithKline
Investigators
Principal Investigator: Sunil Badve, MD Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00857714     History of Changes
Other Study ID Numbers: 0812-11
Study First Received: March 6, 2009
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
DCIS
breast

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

ClinicalTrials.gov processed this record on July 31, 2014