Erlotinib in Treating Patients With Breast Cancer That Can Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00633750
Recruitment Status : Completed
First Posted : March 12, 2008
Results First Posted : September 5, 2012
Last Update Posted : September 5, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Carlos L. Arteaga, Vanderbilt-Ingram Cancer Center

Brief Summary:

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with breast cancer that can be removed by surgery.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: erlotinib hydrochloride Genetic: TUNEL assay Genetic: protein expression analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: matrix-assisted laser desorption ionization mass spectrometry Procedure: therapeutic conventional surgery Phase 2

Detailed Description:



  • To determine the in situ antitumor effect of neoadjuvant erlotinib hydrochloride as measured by a reduction in Ki67 and/or an increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive tumor cells in patients with treatment-naive, operable breast cancer.


  • To identify a molecular profile, based on measurements of Estrogen Receptor (ER), Epidermal Growth Factor Receptor (EGFR), and a Human Epithelial Growth Factor Receptor-2(HER2), and protein expression profiles in patients with treatment-naïve, operable breast cancer that is responsive to erlotinib hydrochloride.
  • To correlate tumor concentrations of erlotinib hydrochloride with serum levels immediately before surgery.

OUTLINE: This is a multi-center study.

Patients receive oral erlotinib hydrochloride once daily for 5-14 days. Patients then undergo surgical resection within 24 hours after the last dose of erlotinib hydrochloride.

Tumor tissue samples are collected at baseline and during surgery for correlative laboratory studies. Tissue samples are stained for ER, HER2, and EGFR levels, proliferation (Ki67), and apoptosis (TUNEL) by immunohistochemistry. Levels of erlotinib hydrochloride in tissue samples are measured by matrix-assisted laser desorption/ionization mass spectrometry. Blood samples are collected on the day of surgery. Levels of erlotinib hydrochloride in blood samples are measured by liquid chromatography/mass spectrometry.

Patients are followed within 6 weeks after surgery.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of OSI-774 (Tarceva), a Human Epidermal Growth Factor (HER) (erbB, Also Known as Epidermal Growth Factor Receptor, EGFR) Tyrosine Kinase Inhibitor, in Treatment-Naïve Operable Breast Cancer
Study Start Date : August 2002
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Tarceva Drug: erlotinib hydrochloride
Tarceva will be given orally at a dose of 150 mg/day for 5-14 days. Patients are to undergo surgical resection of their tumor within 24 hours of the last dose of Tarceva.
Other Names:
  • OSI-774
  • erlotonib

Genetic: TUNEL assay
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens

Genetic: protein expression analysis
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens

Other: immunohistochemistry staining method
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens

Other: laboratory biomarker analysis
Used to assess level of expression of genetic markers in pre-therapy and surgical specimens

Other: liquid chromatography
Used to determine blood plasma levels of Erlotinib on the day of surgery
Other Name: (LC/MS)

Other: mass spectrometry
Used to determine blood plasma levels of Erlotinib on the day of surgery
Other Name: (LC/MS)

Other: matrix-assisted laser desorption ionization mass spectrometry
After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue
Other Name: MALDI MS

Procedure: therapeutic conventional surgery
Surgical treatment will occur within 24-hours following completion of therapy.

Primary Outcome Measures :
  1. Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva [ Time Frame: 5-14 days ]
    In situ anti-tumor effect of Tarceva as measured by a minimum 75% reduction in Ki67 compared to pre-treatment tumor cells in patients with operable breast cancer.

Secondary Outcome Measures :
  1. Molecular Profile of Participants Who Are Responsive to Tarceva [ Time Frame: at 5-14 days ]
    Determined by estrogen receptor status (ER) and human epidermal growth factor receptor 2 (HER2) status, which are measured by staining of 200-500 tumor cells and noting the number stained. Positive = > 10% of cell show staining, negative = < 10% of cells show staining

  2. Average Post-treatment Plasma Level of Erlotinib Hydrochloride [ Time Frame: After last dose of Tarceva, at 5-14 days, and before surgery ]
    Post-treatment plasma level in µmol/L of erlotinib hydrochloride

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical stage I or II (T1 or T2, N0 or N1) invasive mammary carcinoma

    • Diagnosis may be made by fine needle aspiration cytology or core biopsy

      • A repeat core biopsy is not required for patients who have a paraffin embedded diagnostic core biopsy specimen available for immunohistochemical staining

Exclusion Criteria:

  • Patients with locally advanced disease who are planning to undergo preoperative neoadjuvant therapy are not eligible*

    • Locally advanced disease includes any of the following:

      • Primary tumor ≥ 5 cm (T3)
      • Tumor of any size with direct extension to the chest wall or skin (T4a-c)
      • Inflammatory breast cancer (T4d)
      • Fixed axillary lymph node metastases (N2)
      • Metastasis to ipsilateral internal mammary node (N3) NOTE: *Patients with primary tumors ≥ 5 cm (T3) or tumors involving the chest wall or skin who are not candidates for preoperative chemotherapy or who decline preoperative chemotherapy are eligible
  • Measurable residual tumor at the primary site

    • Measurable disease is defined as any mass that can be reproducibly measured by physical examination
  • Planning to undergo surgical treatment with either segmental resection or total mastectomy
  • Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer
  • No locally recurrent breast cancer
  • No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
  • Hormone receptor status not specified


  • Menopausal status not specified
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • ANC ≥ 1,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Serum glutamic oxaloacetic transminase (SGOT) and serum glutamic pyruvic transminase (SGPT) ≤ 1.5 times ULN
  • Must be at least 18 years old
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical illness that, in the judgement of the treating physician, places the patient at high risk of operative mortality


  • See Disease Characteristics
  • No prior chemotherapy for this primary breast cancer
  • At least 7 days since prior tamoxifen or raloxifene as a preventive agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00633750

United States, Alabama
University of Alabama, Birmingham
Birmingham, Alabama, United States, 35249
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27514
United States, Tennessee
Meharry Medical College
Nashville, Tennessee, United States, 37208
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Study Chair: Carlos L. Arteaga, MD Vanderbilt-Ingram Cancer Center

Responsible Party: Carlos L. Arteaga, Professor of Medicine and Cancer Biology, Associate Director of Clinical Research, Director VICC Breast Program, Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT00633750     History of Changes
Other Study ID Numbers: VICC BRE 0222
P50CA098131 ( U.S. NIH Grant/Contract )
R01CA080195 ( U.S. NIH Grant/Contract )
First Posted: March 12, 2008    Key Record Dates
Results First Posted: September 5, 2012
Last Update Posted: September 5, 2012
Last Verified: July 2012

Keywords provided by Carlos L. Arteaga, Vanderbilt-Ingram Cancer Center:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action