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

• ClinicalTrials.gov Identifier: NCT00503841
• Recruitment Status: Terminated
• First Posted: July 19, 2007
• Results First Posted: February 12, 2013
• Last Update Posted: April 30, 2019
• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Elaina Gartner, Barbara Ann Karmanos Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: erlotinib hydrochloride; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy; Procedure: conventional surgery; Procedure: neoadjuvant therapy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: December 2007
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]
2. Effect of Erlotinib Hydrochloride on Tumor Cell Proliferation (Ki67) and Apoptosis (TUNEL) [ Time Frame: Baseline and day 0 ]
3. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes 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

Locations

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201-1379

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elaina M. Gartner, MD; Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database 

• Responsible Party: Elaina Gartner, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00503841
• Obsolete Identifiers: NCT01654757
• Other Study ID Numbers: CDR0000554965; P30CA022453 ( U.S. NIH Grant/Contract ); WSU-2006-138
• First Posted: July 19, 2007
• Results First Posted: February 12, 2013
• Last Update Posted: April 30, 2019
• Last Verified: April 2019

Keywords provided by Elaina Gartner, 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 Hydrochloride; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action