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

This study has been terminated.
(All enrolled participants were screen failures, no data were collected for outcome measures.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Elaina Gartner, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00503841
First received: July 17, 2007
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Breast Cancer
Drug: erlotinib hydrochloride
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of the Effect of Erlotinib (Tarceva®) on Biomarkers in Estrogen Receptor Negative Breast Cancer Expressing the Epidermal Growth Factor Receptor and Interleukin 1α

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Effect of Erlotinib Hydrochloride on Tumor Cell Proliferation (Ki67) and Apoptosis (TUNEL) [ Time Frame: Baseline and day 0 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: December 2007
Study Completion Date: May 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: erlotinib 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.
Drug: erlotinib 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.
Other Names:
  • CP-358,774
  • Erlotinib
  • OSI-774
  • Tarceva
Other: immunohistochemistry staining method
Assessed at the time of the initial biopsy and at the time of surgery.
Other: laboratory biomarker analysis
Correlative studies
Procedure: biopsy
14 days prior to surgery
Procedure: conventional surgery
14 days after taking study drug erlotinib hydrochloride.
Procedure: neoadjuvant therapy
14 days after taking study drug erlotinib hydrochloride.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00503841

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Elaina M. Gartner, MD Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Elaina Gartner, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00503841     History of Changes
Obsolete Identifiers: NCT01654757
Other Study ID Numbers: CDR0000554965, P30CA022453, WSU-2006-138
Study First Received: July 17, 2007
Results First Received: January 9, 2013
Last Updated: March 27, 2013
Health Authority: United States: Federal Government

Keywords provided by Barbara Ann Karmanos Cancer Institute:
stage I breast cancer
recurrent breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014