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

Phase 2

Completed

Conditions: Breast Cancer

Interventions: 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

Registration Number: NCT00633750

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tarceva	TUNEL assay	-
Tarceva	erlotinib hydrochloride	-
Tarceva	protein expression analysis	-
Tarceva	immunohistochemistry staining method	-
Tarceva	laboratory biomarker analysis	-
Tarceva	mass spectrometry	-
Tarceva	matrix-assisted laser desorption ionization mass spectrometry	-
Tarceva	liquid chromatography	-
Tarceva	therapeutic conventional surgery	-

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva	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

Name	Time	Method
Molecular Profile of Participants Who Are Responsive to Tarceva	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
Average Post-treatment Plasma Level of Erlotinib Hydrochloride	After last dose of Tarceva, at 5-14 days, and before surgery	Post-treatment plasma level in µmol/L of erlotinib hydrochloride

Trial Locations

Locations (5): Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Alabama, Birmingham
🇺🇸
Birmingham, Alabama, United States
Meharry Medical College
🇺🇸
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States