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

NCT ID: NCT00633750

Last Updated: 2012-09-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-08-31

Study Completion Date

2007-10-31

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Keywords

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stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tarceva

Group Type EXPERIMENTAL

erlotinib hydrochloride

Intervention Type DRUG

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.

TUNEL assay

Intervention Type GENETIC

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

protein expression analysis

Intervention Type GENETIC

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

immunohistochemistry staining method

Intervention Type OTHER

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

laboratory biomarker analysis

Intervention Type OTHER

Used to assess level of expression of genetic markers in pre-therapy and surgical specimens

liquid chromatography

Intervention Type OTHER

Used to determine blood plasma levels of Erlotinib on the day of surgery

mass spectrometry

Intervention Type OTHER

Used to determine blood plasma levels of Erlotinib on the day of surgery

matrix-assisted laser desorption ionization mass spectrometry

Intervention Type OTHER

After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue

therapeutic conventional surgery

Intervention Type PROCEDURE

Surgical treatment will occur within 24-hours following completion of therapy.

Interventions

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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.

Intervention Type DRUG

TUNEL assay

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

Intervention Type GENETIC

protein expression analysis

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

Intervention Type GENETIC

immunohistochemistry staining method

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

Intervention Type OTHER

laboratory biomarker analysis

Used to assess level of expression of genetic markers in pre-therapy and surgical specimens

Intervention Type OTHER

liquid chromatography

Used to determine blood plasma levels of Erlotinib on the day of surgery

Intervention Type OTHER

mass spectrometry

Used to determine blood plasma levels of Erlotinib on the day of surgery

Intervention Type OTHER

matrix-assisted laser desorption ionization mass spectrometry

After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue

Intervention Type OTHER

therapeutic conventional surgery

Surgical treatment will occur within 24-hours following completion of therapy.

Intervention Type PROCEDURE

Other Intervention Names

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OSI-774 erlotonib (LC/MS) (LC/MS) MALDI MS

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Carlos L. Arteaga

Professor of Medicine and Cancer Biology, Associate Director of Clinical Research, Director VICC Breast Program, Medical Oncologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carlos L. Arteaga, MD

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

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University of Alabama, Birmingham

Birmingham, Alabama, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Meharry Medical College

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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VU-VICC-BRE-0222

Identifier Type: -

Identifier Source: secondary_id

VU-VICC-020448

Identifier Type: -

Identifier Source: secondary_id

P50CA098131

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA080195

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VICC BRE 0222

Identifier Type: -

Identifier Source: org_study_id