Breast Cancer
Conditions
Keywords
stage I breast cancer, recurrent breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This clinical trial is studying how well erlotinib works in treating women undergoing surgery for stage I, stage II, or stage III breast cancer.
Detailed description
OBJECTIVES: Primary * To estimate the effect of erlotinib hydrochloride on expression of interleukin (IL)-1α in patients with estrogen receptor (ER-)-negative, EGFR-positive and IL-1α-positive breast cancer. Secondary * To estimate the effect of erlotinib hydrochloride on expression of nuclear NF-κB and amphiregulin (AR) in patients with ER-negative, EGFR-positive and IL-1α-positive breast cancer. * To estimate the effect of erlotinib on tumor cell proliferation (Ki67) and apoptosis (TUNEL). * To estimate the rates of IL-1α, nuclear NF-κB, and AR expression in patients with ER-negative, EGFR-positive breast cancer. * To follow the clinical course of patients with resectable ER-negative, EGFR-positive and IL-1α-positive breast cancer. * To assess the toxicity of a 15-day regimen of daily oral administration of erlotinib hydrochloride in participants with ER-negative, EGFR-positive and IL-1α-positive breast cancer. OUTLINE: This is an open-label, pilot study. Patients are stratified according to HER2 status (positive vs negative). Patients receive oral erlotinib hydrochloride once daily on days -14 to 0 in the absence of disease progression or unacceptable toxicity. Patients undergo surgery on day 0. Tissue samples are collected at baseline and examined for expression of estrogen receptor, progesterone receptor, HER2, EGFR, interleukin (IL)-1α, amphiregulin, and NF-kB. Tissue samples collected at surgery are examined for IL-1α, NF-kB, and amphiregulin by IHC. Following surgery, patients will be contacted 1 week post-surgery (± 1 day) or 1 week post-withdrawal from study (± 1 day) by phone call or clinic visit to assess toxicity. After that, patients will be followed and treated according to standard of care practices. If patients choose to follow-up with an oncologist outside of our institution, they or their oncologist will be contacted every 6 months for updated information on their conditions.
Interventions
DRUGerlotinib hydrochloride
Patients receive erlotinib hydrochloride PO (orally) QD (every day) on days -14-0 immediately prior to scheduled surgery. Treatment continues in the absence of disease progression or unacceptable toxicity.
OTHERimmunohistochemistry staining method
Assessed at the time of the initial biopsy and at the time of surgery.
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREbiopsy
14 days prior to surgery
PROCEDUREconventional surgery
14 days after taking study drug erlotinib hydrochloride.
PROCEDUREneoadjuvant therapy
14 days after taking study drug erlotinib hydrochloride.
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion * Cytologically or histologically confirmed adenocarcinoma of the breast * Stage I-III disease * BI-RADS 4 or 5 abnormalities on breast imaging and undergoing core needle biopsy for diagnosis * Participants must have a lesion of at least 1-cm on breast imaging studies (mammogram, ultrasound, or MRI) * Participants must have breast cancer amenable to surgery with curative intent and must have agreed to undergo such surgery * The surgical procedure must be scheduled in the near future to accommodate a treatment period of no less and no more than 15 days * Clinically positive for the overexpression of EGFR and interleukin-1α * Clinically negative for expression of the estrogen receptor (ER-negative) and progesterone receptor (PgR-negative) * May be positive or negative for HER2 Exclusion * Locally advanced or metastatic disease not amenable to surgery * Known brain metastases PATIENT CHARACTERISTICS: Inclusion * Female * Menopausal status not specified * ECOG performance status (PS) 0-2 or Karnofsky PS 60-100% * ANC ≥ 1000/mm³ * Platelet count ≥ 75,000/mm³ * AST and ALT ≤ 2.5 times upper limits of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Bilirubin ≤ 2 times ULN * Hemoglobin \> 9 g/dL * Creatinine within normal institutional limits OR creatinine clearance \>60 mL/min * Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and women within 6 months of menopause * Women of child-bearing potential and their partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Exclusion * Pregnant or nursing * History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride * Uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: Exclusion * Received any other therapy (i.e., surgery, radiation, hormone treatment, biologic therapy, and/or chemotherapy) for the treatment of breast cancer * Concurrent use of anti-neoplastic or anti-tumor agents not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy * Receiving any other investigational agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of Erlotinib Hydrochloride on Expression of IL-1a in Patients With ER- Negative, EGFR- Positive and (IL-)1a-positive Breast Cancer | Baseline and day 0 |
Secondary
| Measure | Time frame |
|---|---|
| Effect of Erlotinib Hydrochloride on Expression of NF-κB and AR in Patients With ER-negative, EGFR-positive and IL-1a-positive Breast Cancer | Baseline and day 0 |
| Effect of Erlotinib Hydrochloride on Tumor Cell Proliferation (Ki67) and Apoptosis (TUNEL) | Baseline and day 0 |
| Toxicity of a 15-day Regimen of Daily Oral Administration of Erlotinib Hydrochloride | At day -7, prior to surgery, and 1 week post-surgery |
Countries
United States
Participant flow
Recruitment details
44 participants signed consent starting 1-9-08 and recruitment ending with the last participant signing on 1-19-10. All participants enrolled onto screening portion of study, but none were ever put onto the treatment portion of the study.
Pre-assignment details
All participants that signed consent were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Hydrochloride If participants would have went onto study they would receive erlotinib hydrochloride PO (orally) QD (every day) on days -14-0 immediately prior to scheduled surgery. Treatment continues in the absence of disease progression or unacceptable toxicity. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | All screen failures | 44 |
Baseline characteristics
| Characteristic | Erlotinib Hydrochloride |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age, Continuous | 52 years |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 44 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 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Effect of Erlotinib Hydrochloride on Expression of IL-1a in Patients With ER- Negative, EGFR- Positive and (IL-)1a-positive Breast Cancer
Time frame: Baseline and day 0
Population: No participants received the study drug erlotinib hydrochloride.
Secondary
Effect of Erlotinib Hydrochloride on Expression of NF-κB and AR in Patients With ER-negative, EGFR-positive and IL-1a-positive Breast Cancer
Time frame: Baseline and day 0
Population: No data collected for secondary hypotheses.
Secondary
Effect of Erlotinib Hydrochloride on Tumor Cell Proliferation (Ki67) and Apoptosis (TUNEL)
Time frame: Baseline and day 0
Population: No data collected for secondary hypotheses.
Secondary
Toxicity of a 15-day Regimen of Daily Oral Administration of Erlotinib Hydrochloride
Time frame: At day -7, prior to surgery, and 1 week post-surgery
Population: No data collected for secondary hypotheses.