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Lapatinib and Trastuzumab With or Without Endocrine Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Baylor Breast Care Center
ClinicalTrials.gov Identifier:
NCT00548184
First received: October 19, 2007
Last updated: June 6, 2012
Last verified: June 2012
History of Changes
  Purpose

We think that lapatinib will help to shrink your tumor when given prior to the main or primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is given before the main or primary therapy, it is called neoadjuvant therapy. We will compare lapatinib with lapatinib plus trastuzumab (herceptin) for 12 weeks. If your tumor is estrogen receptor positive (ER positive), estrogen deprivation will also be given to you. Tumors that are ER positive have a lot of estrogen receptors found in them. This is also called "over expression" or amplification of estrogen receptors.

The most important information we will get from this study is to see the response to "neoadjuvant" (treatment given before the main treatment), lapatinib with trastuzumab (herceptin) in your tumor tissue sample.


Condition Intervention Phase
Breast Cancer
 Drug: Lapatinib
Drug: Trastuzumab
Drug: Endocrine
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Baylor Breast Care Center:

Primary Outcome Measures:
  • Pathologic Assessment After Study Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Pathologic Assessment After 12 weeks of lapatinib and trastuzumab with or without endocrine therapy. Pathologic complete response: no invasive cancer in the residual breast. Near pathologic complete response: residual disease of less than 1 cm in breast.


Secondary Outcome Measures:
  • Data Analysis of the Biomarkers: Immunohistochemical Staining of Cells From Breast Biopsies and Skin Biopsies Will be Performed. [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: September 2008
Estimated Study Completion Date: January 2013
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lapatinib
    Monoclonal antibody
    Other Name: TyKerb
    Drug: Trastuzumab
    Monoclonal antibody
    Other Name: Herceptin
    Drug: Endocrine
    Hormonal Therapy
    Other Name: Varies
Detailed Description:

The neoadjuvant setting is especially attractive for studies of predictive biologic correlates for several reasons including early assessment of response to therapy, access to the primary tumor, and reduced patient numbers compared to those required in the adjuvant setting. Response to neoadjuvant therapy is a validated surrogate marker for improved survival; it may be used to test the overall efficacy of neoadjuvant treatment regimens and response in the primary tumor mirrors the effect of therapy on micrometastases.

Trastuzumab is an efficacious agent in HER2 overexpressing breast cancers. Our results with neoadjuvant trastuzumab indicate that its efficacy may be better in patients with treatment-naïve tumors compared to metastatic disease, with 26% of patients showing a partial response after only 3 weeks of therapy. No patients progressed during this 3-week period. We have also conducted a neoadjuvant lapatinib study given as a single agent for 6 weeks. The response rates in this second study have been impressive with greater than 80% responses in patients with HER2 positive locally advanced breast cancers. It is likely that the true response rate to HER2 blockade would be higher had therapy been continued for longer. We therefore hypothesize that lapatinib, a dual tyrosine kinase inhibitor, together with trastuzumab, will result in tumor regression when given as neoadjuvant therapy in HER2 overexpressing breast cancer. We will compare lapatinib plus trastuzumab for 12 weeks, and if the tumors express ER, estrogen deprivation will also be administered.

This is a phase II trial. Clinical efficacy will be assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 12. Objective tumor response rate defined as objective bidimensional tumor measurements after neoadjuvant treatment at 12 weeks will be calculated, and assessed according to standard RECIST criteria. Pathologic responses will be graded as pathologic complete response if there is no invasive cancer in the residual breast at the time of surgery. Near pathologic complete response will also be documented as residual disease of less than 1 cm.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must be female.
  • Signed informed consent.
  • Locally advanced breast cancers or primary breast cancers are eligible. Locally advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary nodal involvement. (If tumors are less than 3 cm, we will use radiologically measured tumor size to determine the minimal tumor size for eligibility and in assessing tumor size during follow-up).
  • HER2 overexpressing tumors defined as HercepTest score of 3+, or > 10% cells moderately or strongly HER2 positive by other methods, or Allred semi-quantitative score of >5, or gene amplified.
  • Negative serum pregnancy test (HCG) within 7 days of starting study, if of child-bearing potential.
  • Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.
  • Performance status (WHO scale) less than 2 and life expectancy more than 6 months.
  • Age at least 18 years.
  • No brain or leptomeningeal disease.
  • No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.

Note: The presence of pathological involvement of axillary nodes will be assessed and agreed upon by two investigators.

Exclusion Criteria:

  • Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
  • Severe underlying chronic illness or disease.
  • Cardiomyopathy or baseline LVEF less than 50%.
  • Other investigational drugs while on study.
  • Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded
  • Taking any lapatinib-prohibited medication within 7 days of first dose of study medications. (See Prohibited Medications List in protocol.)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00548184

Locations
United States, Alabama
UAB Cancer Center
Birmingham, Alabama, United States, 35294
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bunting-Blaustein Cancer Research
Baltimore, Maryland, United States, 21231-1000
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6868
United States, Texas
Baylor College of Medicine, Lester and Sue Smith Breast Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor Breast Care Center
GlaxoSmithKline
Investigators
Principal Investigator: Mothaffar Rimawi, MD Baylor Breast Center
  More Information

No publications provided

Responsible Party: Baylor Breast Care Center
ClinicalTrials.gov Identifier: NCT00548184     History of Changes
Other Study ID Numbers: H-20464
Study First Received: October 19, 2007
Results First Received: May 1, 2012
Last Updated: June 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Breast Care Center:
primary breast cancers
Locally advanced breast cancers

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Lapatinib
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013