Clinical trial NCT00633750: Erlotinib in Treating Patients With Breast Cancer That Can Be Removed by Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva
timeFrame: 5-14 days
Secondary outcomes:
measure: Molecular Profile of Participants Who Are Responsive to Tarceva
timeFrame: at 5-14 days
measure: Average Post-treatment Plasma Level of Erlotinib Hydrochloride
timeFrame: After last dose of Tarceva, at 5-14 days, and before surgery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Carlos L. Arteaga, MD
role: STUDY_CHAIR
References: