Phase II Open-Label Trial of Tarceva in Women With Metastatic, Hormone- and HER2-Negative Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Erlotinib
Intervention description: During the treatment period, subjects will receive single agent erlotinib, 150mg/day.
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
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic breast cancer; ER and PR hormone receptor negative; HER2/neu negative; EGFR positive

Summary:

      The goal of this trial is to determine the activity of erlotinib in a rationally selected
      population of women with ER-negative, PR-negative, HER2/neu-negative, EGFR-positive breast
      cancer. If erlotinib is shown to have activity, this could identify a form of targeted
      therapy for this specific subset of breast cancer patients. In addition, it may identify a
      subset of breast cancer patients with tumors that overexpress EGFR in whom other EGFR
      targeted therapies could warrant further testing.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Verbal and written informed consent to participate in the study.

          2. Women greater than or equal to 18 years of age.

          3. Histologically documented metastatic or locally advanced, incurable breast cancer with
             a tumor block available

          4. Less than or equal to 1 prior chemotherapy for metastatic or locally unresectable
             disease.

          5. Prior treatment with anthracycline and taxane chemotherapy, either in the adjuvant or
             metastatic setting

          6. Measurable disease on CT or PET scan or physical exam Disease at a previously
             irradiated site is considered measurable if there is clear evidence of disease
             progression following radiation therapy.

          7. ER-negative, PR-negative and HER2-neu-negative. Estrogen and progesterone status will
             be defined by immunohistochemistry. Her2/neu status will be considered negative if the
             ratio of the number of copies of the Her2/neu gene to the centromeric probe for
             chromosome 17 is approximately 1. This will be done by FISH (fluorescent in-situ
             hybridization) testing.

          8. EGFR-positive defined as strong membrane staining in greater than 10% of tumor cells
             by immuno-histochemistry (Dako).

          9. Pre- or post-menopausal.

         10. ECOG performance status of 0 - 2.

         11. Life expectancy of greater than or equal to 3 months.

         12. Use of barrier contraceptive methods in women of childbearing potential.

         13. Ability to comply with study and follow-up procedures.

        Exclusion Criteria:

          1. Pleural effusions or blastic bone lesions as the only manifestations of the current
             metastatic breast cancer.

          2. Other primary malignancies within 5 years except for adequately treated carcinoma in
             situ of the cervix or basal or squamous cell skin cancer.

          3. Symptomatic or untreated brain metastases. Subjects are eligible if they are
             neurologically stable after treatment for brain metastases and have been off steroids
             for greater than or equal to 4 weeks.

          4. Radiotherapy, immunotherapy, hormonal therapy or chemotherapy within 21 days prior to
             registration.

          5. Prior treatment with an agent that targets the EGFR or the EGFR-specific tyrosine
             kinase activity.

          6. Unstable systemic disease, including active infection, uncontrolled hypertension,
             unstable angina, congestive heart failure, or myocardial infarction within 6 months
             prior to Day 0, or serious cardiac arrhythmias requiring medication.

          7. Major surgery, biopsy of a parenchymal organ, or significant traumatic injury
             occurring within 21 days prior to Day 0.

          8. History of other diseases, metabolic dysfunction, physical examinations findings, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that might affect the
             interpretation of the results of the study or render the patient at high risk from
             treatment complications.

          9. Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, prior surgical procedures affecting absorption, or
             active peptic ulcer disease.

         10. Pregnancy or lactation. A negative serum or urine pregnancy test is required for women
             of child-bearing potential during screening and within 7 - 10 days of Day 1 of Cycle 1
             of erlotinib (Tarcevo®)administration. Men and premenopausal women of child bearing
             potential will follow an approved, medically accepted birth control regimen while
             taking erlotinib and for 30 days following the last dose of study drug.

         11. Active infection requiring parenteral antibiotics.

         12. Any of the following abnormal baseline hematologic values:

               -  Granulocyte count less than or equal to 1500/μL

               -  Platelet count less than or equal to 100,000/μL

               -  Hemoglobin less than or equal to 9g/dl (transfusion permitted)

         13. Any of the following abnormal baseline liver function tests:

               -  Serum bilirubin greater than or equal to 1.5x upper limit of normal (ULN)

               -  Serum ALT and AST greater than or equal to 2.5x ULN (greater than 5x ULN if due
                  to liver metastases)

               -  Alkaline phosphatase greater than or equal to 2.5x ULN (greater than 4x ULN if
                  due to liver or bone metastases)

         14. Other baseline laboratory values:

               -  Serum creatinine greater than or equal to 1.5x ULN or creatinine clearance less
                  than or equal to 60mL/min

               -  Uncontrolled hypercalcemia (greater than 11.5mg/dL)