Lapatinib and Trastuzumab With or Without Endocrine Therapy

NCT00548184 | Completed Phase 2 Results DMC

• 1 other identifier: H-20464
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 6

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.

Conditions

Breast Cancer

Keywords

primary breast cancers; Locally advanced breast cancers

Outcome Measures

Primary Outcomes (1)

• Pathologic Assessment After Study Treatment

  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.

  12 weeks

Other Outcomes (1)

• Data Analysis of the Biomarkers: Immunohistochemical Staining of Cells From Breast Biopsies and Skin Biopsies Will be Performed.

  one year

Study Arms (1)

Single Group Assignment

EXPERIMENTAL

Lapatinib Trastuzumab Endocrine

Drug: Lapatinib; Drug: Trastuzumab; Drug: Endocrine

Interventions

Lapatinib DRUG

Monoclonal Antibody

Also known as: TyKerb

Single Group Assignment

Trastuzumab DRUG

Monoclonal Antibody

Also known as: Herceptin

Single Group Assignment

Endocrine DRUG

Hormonal Therapy

Also known as: Varies

Single Group Assignment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Baylor Breast Care Center: lead
• GlaxoSmithKline: collaborator

Study Sites (6)

UAB Cancer Center

Birmingham, Alabama, 35294, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bunting-Blaustein Cancer Research

Baltimore, Maryland, 21231-1000, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6868, United States

Location

Baylor College of Medicine, Lester and Sue Smith Breast Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 30903140 DERIVED

• 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.

  PMID: 23569315 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Mothaffar Rimawi
• Organization: Baylor College of Medicine

rimawi@bcm.edu

713-798-1311

Study Officials

• Mothaffar Rimawi, MD

  Baylor Breast Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: October 19, 2007
• First Posted: October 23, 2007
• Study Start: May 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2014
• Last Updated: November 7, 2019
• Results First Posted: June 1, 2012

Record last verified: 2019-10

Locations

US (6)