Breast Cancer
Conditions
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer
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.
Interventions
DRUGerlotinib 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.
GENETICTUNEL assay
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
GENETICprotein expression analysis
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
OTHERimmunohistochemistry staining method
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
OTHERlaboratory biomarker analysis
Used to assess level of expression of genetic markers in pre-therapy and surgical specimens
Used to determine blood plasma levels of Erlotinib on the day of surgery
OTHERmass spectrometry
Used to determine blood plasma levels of Erlotinib on the day of surgery
OTHERmatrix-assisted laser desorption ionization mass spectrometry
After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue
PROCEDUREtherapeutic conventional surgery
Surgical treatment will occur within 24-hours following completion of therapy.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment period = 8/28/2002 through 10/16/2007
Pre-assignment details
54 participants were initially consented for this study. Four were determined to be ineligible. Three participants withdrew from the study before beginning.
Participants by arm
| Arm | Count |
|---|---|
| Tarceva Tarceva given by mouth at a dose of 150 mg/day for 5-14 days. Participants are to undergo surgical resection of their tumor within 24 hours of the last dose of Tarceva. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Tarceva |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age Continuous | 56 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 47 |
| serious Total, serious adverse events | 1 / 47 |
Outcome results
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.
Time frame: 5-14 days
Population: Patients who received the study drug and who had available pre- and post-treatment tissue.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tarceva | Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva | 8 participants |
Secondary
Average Post-treatment Plasma Level of Erlotinib Hydrochloride
Post-treatment plasma level in µmol/L of erlotinib hydrochloride
Time frame: After last dose of Tarceva, at 5-14 days, and before surgery
Population: Participants with blood taken within 24 hours of last dose of erlotinib and before surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tarceva | Average Post-treatment Plasma Level of Erlotinib Hydrochloride | 8.8 µmol/L | Standard Deviation 7.4 |
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
Time frame: at 5-14 days
Population: Participants with available pre- and post-treatment tissue and who demonstrated a post-treatment decrease in Ki67 levels compared to their pre-treatment levels
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tarceva | Molecular Profile of Participants Who Are Responsive to Tarceva | Estrogen receptor positive | 6 participants |
| Tarceva | Molecular Profile of Participants Who Are Responsive to Tarceva | Estrogen receptor negative | 2 participants |
| Tarceva | Molecular Profile of Participants Who Are Responsive to Tarceva | HER-2 positive | 1 participants |
| Tarceva | Molecular Profile of Participants Who Are Responsive to Tarceva | HER-2 negative | 7 participants |