Phase II Study of Erlotinib, an EGFR Inhibitor in Metastatic EGFR-positive 'Triple Receptor-negative' Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Tarceva
Intervention description: Tarceva (erlotinib hydrochloride) given alone, at 150 mg by mouth daily.
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: Female
Healthy volunteers: No
Keywords: Breast cancer; Carcinoma of the breast; Stage IV; Triple receptor-negative; Triple receptor-negative breast cancer; Metastatic triple receptor-negative breast cancer; Epidermal growth factor receptor; EGFR; EGFR-overexpressing; GFR inhibitor erlotinib; Erlotinib hydrochloride; Erlotinib; Tarceva; OSI-774

Summary:

      The goal of this clinical research study is to learn if Tarceva® (erlotinib hydrochloride)
      can help control triple receptor-negative breast cancer. The safety of this drug will also be
      studied.

      Objectives:

      To assess the clinical efficacy, biologic effects and safety of the EGFR inhibitor erlotinib
      in the treatment of patients with 'triple receptor-negative' metastatic carcinoma of the
      breast.

      Primary endpoints:

      1) Time to progression (TTP)

      Secondary endpoints:

        1. clinical benefit rate as defined by complete and partial response and stable disease

        2. overall survival (OS)

        3. safety profile and tolerability of erlotinib

        4. biologic correlative studies
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologic confirmation of metastatic (stage IV) 'triple
             receptor-negative' breast cancer. Tissue must be available at baseline or agree to
             biopsy. The diagnosis of 'triple receptor-negative' breast cancer requires that either
             the primary tumor or a metastatic deposit be shown to be negative for estrogen
             receptors (ER) and progesterone receptors (PR) by immunohistochemistry (IHC) and for
             HER2/neu by IHC (i.e. a score of 0 and 1+) or fluorescent in situ hybridization
             (FISH).

          2. EGFR protein expression and gene copy number will be evaluated on stored tissue sample
             at a later time. Unstained slides, a block, or agreement for biopsy is required for
             study participation.

          3. Patients with metastatic breast cancer to any distant site are eligible once their
             disease is clinically/radiologically measurable

          4. Patients must have disease which is resistant to taxanes and anthracyclines. There is
             no limit to the number of previous therapies for metastatic disease.

          5. Patients are eligible if they have not had prior exposure to an EGFR inhibitor
             (e.g.Gefitinib, Erlotinib) or antibody (e.g. Cetuximab).

          6. Availability of tissue blocks and/or fresh/frozen tumor samples is an eligibility
             requirement in order to run the EGFR IHC, FISH and to confirm, if needed ER, PR and
             HER2/neu status.

          7. Patients may, but are not required, to have a repeat tumor biopsy performed on study
             entry prior to beginning therapy and also early during study therapy for correlative
             studies.

          8. Patients with 'triple receptor-negative' metaplastic breast cancers are eligible if
             they meet the criterion of EGFR overexpression.

          9. Patients must sign an informed consent indicating that they are aware of the
             investigational nature of the study, in keeping with institutional policy

         10. Patients must have tissue blocks available from previous primary tumor surgery or
             biopsy or from a previous biopsy of metastatic disease for EGFR status assessment and
             for correlative studies

         11. Patients should have adequate bone marrow function, as defined by peripheral
             granulocyte count of >/= 1500/mm^3, and a platelet count >/= 100000/ mm^3. Patients
             must have adequate liver function with a bilirubin within 1.5 times the upper limit of
             normal (ULN). Transaminases (SGPT) may be up to 5 * the ULN and alkaline phosphatase
             may be up to 5 * ULN

         12. Patients should have adequate renal function (serum creatinine </= 1.5 times the ULN)

         13. Negative pregnancy test for a woman of childbearing potential

         14. Women of childbearing potential must use a reliable and appropriate contraceptive
             method during the study

         15. Patients with a performance status of 2 or better by World Health Organization
             (W.H.O.)

        Exclusion Criteria:

          1. Patients with uncompensated congestive cardiac failure are not eligible

          2. Patients with a myocardial infarction in the previous 12 months are not eligible

          3. Patients with central nervous system (CNS) metastases are not eligible

          4. Patients with an organ allograft

          5. Patients with a serious concurrent infection or illness including, but not limited to,
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit
             compliance with study requirements