Lapatinib and Trastuzumab With or Without Endocrine Therapy

• ClinicalTrials.gov Identifier: NCT00548184
• Recruitment Status: Completed
• First Posted: October 23, 2007
• Results First Posted: June 1, 2012
• Last Update Posted: November 7, 2019
• Sponsor: Baylor Breast Care Center
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Mothaffar Rimawi, Baylor Breast Care Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Lapatinib; Drug: Trastuzumab; Drug: Endocrine	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• 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
• Actual Study Start Date: May 2008
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Group Assignment; Lapatinib Trastuzumab Endocrine	Drug: Lapatinib; Monoclonal Antibody; Other Name: TyKerb; Drug: Trastuzumab; Monoclonal Antibody; Other Name: Herceptin; Drug: Endocrine; Hormonal Therapy; Other Name: Varies

Outcome Measures

Primary Outcome Measures :

1. Pathologic Assessment After Study Treatment [ Time Frame: 12 weeks ]
   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.

Other Outcome Measures:

1. Data Analysis of the Biomarkers: Immunohistochemical Staining of Cells From Breast Biopsies and Skin Biopsies Will be Performed. [ Time Frame: one year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Veeraraghavan J, De Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R. A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Ann Oncol. 2019 Jun 1;30(6):927-933. doi: 10.1093/annonc/mdz076.

Rimawi MF, Mayer IA, Forero A, Nanda R, Goetz MP, Rodriguez AA, Pavlick AC, Wang T, Hilsenbeck SG, Gutierrez C, Schiff R, Osborne CK, Chang JC. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol. 2013 May 10;31(14):1726-31. doi: 10.1200/JCO.2012.44.8027. Epub 2013 Apr 8.

• Responsible Party: Mothaffar Rimawi, Medical Director, Baylor Breast Care Center
• ClinicalTrials.gov Identifier: NCT00548184
• Other Study ID Numbers: H-20464
• First Posted: October 23, 2007
• Results First Posted: June 1, 2012
• Last Update Posted: November 7, 2019
• Last Verified: October 2019

Keywords provided by Mothaffar Rimawi, 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, Immunological; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action