Erlotinib in Treating Patients With Breast Cancer That Can Be Removed by Surgery - Full Text View

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:

Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva [ Time Frame: 5-14 days ] [ Designated as safety issue: No ]
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:

Molecular Profile of Participants Who Are Responsive to Tarceva [ Time Frame: at 5-14 days ] [ Designated as safety issue: No ]
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
Average Post-treatment Plasma Level of Erlotinib Hydrochloride [ Time Frame: After last dose of Tarceva, at 5-14 days, and before surgery ] [ Designated as safety issue: No ]
Post-treatment plasma level in µmol/L of erlotinib hydrochloride

Enrollment:	50
Study Start Date:	August 2002
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Detailed Description:

OBJECTIVES:

Primary

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.

Secondary

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00633750

Locations

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
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Meharry Medical College
Nashville, Tennessee, United States, 37208

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Carlos L. Arteaga, MD

Vanderbilt-Ingram Cancer Center

More Information

No publications provided

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
ClinicalTrials.gov Identifier:	NCT00633750 History of Changes
Other Study ID Numbers:	VICC BRE 0222, VU-VICC-BRE-0222, VU-VICC-020448, P50 CA098131, RO1 CA80195
Study First Received:	March 11, 2008
Results First Received:	May 1, 2012
Last Updated:	August 2, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by 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
Neoplasms
Breast Diseases
Skin Diseases

Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013