Ph II Letrozole + OSI-774 (Tarceva) in Post-menopausal, w/ ER and/or PR-positive Met Breast Cancer.
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: erlotinib hydrochloride; letrozole; fluorescence in situ hybridization; immunohistochemistry staining method; laboratory biomarker analysis
Intervention description: OSI-774 150 mg/day; Letrozole 2.5 mg/day; To determine HER2 gene amplification or excess copies of the HER2 gene; to measure the epidermal growth factor receptors (EGFR); To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs
Intervention MeSH terms: Erlotinib Hydrochloride; Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV breast cancer

Summary:

      RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
      letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells.
      Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Giving letrozole together with erlotinib may kill more tumor cells.

      PURPOSE: This phase II clinical trial is studying how well giving letrozole together with
      erlotinib works in treating postmenopausal women with estrogen receptor-positive and/or
      progesterone receptor-positive locally recurrent or metastatic breast cancer.
    

Eligibility criteria:

        -  Patients must have estrogen (ER) and/or progesterone receptor (PgR)-positive,
             histologically confirmed adenocarcinoma of the breast with measurable (but not
             operable) locally recurrent disease, or measurable and/or evaluable metastatic disease
             (see protocol section 10.3), including isolated bone metastases.

          -  Patients with available paraffin tissue blocks from either the primary or the
             metastatic site must submit tissue blocks for retrospective EGFR and HER2 analysis. If
             tissue blocks cannot be submitted, 20 unstained slides from each paraffin block must
             be submitted.

          -  All patients must be post-menopausal females as defined by one of the following:

               -  Prior bilateral oophorectomy

               -  Prior bilateral ovarian irradiation

               -  No menstrual period for 12 months or longer

               -  If age 55 years or less and < 12 months from last menstrual period, patient must
                  have a serum estradiol < or equal to 30 and an FSH level > 40.

          -  Patients must not have had more than 1 prior chemotherapy regimen for metastatic
             disease and have fully recovered from any grade 2-4 toxicities related to
             chemotherapy. No concurrent chemotherapy is allowed while on protocol therapy.

          -  Patients may have had 1 prior hormonal therapy for metastatic disease. This includes:
             tamoxifen, fulvestrant, anastrozole, exemestane, aminoglutethimide, megace, and
             letrozole. Patients may have received tamoxifen or aromatase inhibitors in the
             adjuvant setting.

          -  Patients must not have had prior therapy with EGF receptor inhibitors.

          -  Previous but not concomitant therapy with trastuzumab (Herceptin) is allowed. Patients
             must not have received Herceptin within 4 weeks of initiation of protocol therapy.

          -  Patients must have an ECOG performance status of 0, 1, or 2.

          -  Patients must have adequate hematologic, hepatic, and renal function as defined by the
             following within 2 weeks of initiation of therapy:

               -  Absolute neutrophils > or equal to 1,500/mm3 and platelets > or equal to
                  100,000/mm3.

               -  Bilirubin < than or equal to 1.5 upper limit of normal.

               -  SGOT and SGPT < or equal to 2.5 upper limit of normal.

               -  Creatinine < or equal to 1.5 upper limit of normal.

               -  INR, PTT and PT in the normal range.

               -  Must be 18 years of age or older.

          -  Patients must not have a history of central nervous system metastases or unevaluated
             CNS symptoms suggestive of possible brain metastases.

          -  Patients may receive concurrent radiation therapy to painful bone metastases or areas
             of impending bone fracture as long as radiation therapy is initiated prior to study
             entry and sites of evaluable disease outside the radiation port(s) are available for
             follow-up. Patients who have received prior radiotherapy must have recovered from
             toxicity induced by this treatment.

          -  Patients < 55 years of age must not have received Luteinizing hormone releasing
             hormone (LHRH) antagonists within 3 months prior to protocol therapy.

          -  Patients must not suffer from medical or psychiatric conditions that would interfere
             with ability to provide informed consent, communicate side effects, or comply with
             protocol requirements including maintenance of a compliance/pill diary.

          -  Patients must be disease-free of prior invasive cancers for > 5 years with the
             exception of basal or squamous cancer of the skin or cervical carcinoma in situ.