Erlotinib in Treating Women Undergoing Surgery For Stage I, Stage II, or Stage III Breast Cancer

Barbara Ann Karmanos Cancer Institute

Status: Terminated

Conditions: Breast Cancer

Treatments: Procedure: conventional surgery; Other: laboratory biomarker analysis; Drug: erlotinib hydrochloride; Procedure: neoadjuvant therapy; Other: immunohistochemistry staining method; Procedure: biopsy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00503841

CDR0000554965

P30CA022453 (U.S. NIH Grant/Contract)

WSU-2006-138

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

erlotinib hydrochloride

Experimental group

Description:

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.

Treatment:

Procedure: conventional surgery

Other: immunohistochemistry staining method

Procedure: biopsy

Other: laboratory biomarker analysis

Procedure: neoadjuvant therapy

Drug: erlotinib hydrochloride