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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00633750
• Other study ID #: VICC BRE 0222
• Secondary ID: VU-VICC-BRE-0222
• Status: Completed
• Phase: Phase 2
• First received: March 11, 2008
• Last updated: August 2, 2012
• Start date: August 2002
• Est. completion date: October 2007

Study information

• Verified date: July 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Genetic:
• TUNEL assay
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
• 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
• laboratory biomarker analysis
Used to assess level of expression of genetic markers in pre-therapy and surgical specimens
• liquid chromatography
Used to determine blood plasma levels of Erlotinib on the day of surgery
• mass spectrometry
Used to determine blood plasma levels of Erlotinib on the day of surgery
• matrix-assisted laser desorption ionization mass spectrometry
After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue

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

Locations

Country	Name	City	State
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Meharry Medical College	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva	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.	5-14 days	No
Secondary	Molecular Profile of Participants Who Are Responsive to Tarceva	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	at 5-14 days	No
Secondary	Average Post-treatment Plasma Level of Erlotinib Hydrochloride	Post-treatment plasma level in µmol/L of erlotinib hydrochloride	After last dose of Tarceva, at 5-14 days, and before surgery	No