Anastrozole and ZD1839 Compared With Fulvestrant and ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer
Condition: Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: anastrozole; gefitinib; fulvestrant; laboratory biomarker analysis
Intervention description: Given orally; Given orally; Given intramuscularly; Correlative studies
Intervention MeSH terms: Fulvestrant; Anastrozole; Gefitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying how well giving gefitinib together with
      anastrozole works compared to giving gefitinib together with fulvestrant in treating
      postmenopausal women with recurrent or metastatic breast cancer. Estrogen can stimulate the
      growth of breast cancer cells. Hormone therapy using anastrozole and fulvestrant may fight
      breast cancer by blocking the use of estrogen. Gefitinib (ZD1839) may stop the growth of
      cancer cells by blocking the enzymes necessary for their growth. It is not yet known whether
      gefitinib is more effective when combined with anastrozole or fulvestrant in treating breast
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have estrogen and/or progesterone receptor positive histologically
             confirmed adenocarcinoma of the breast with measurable recurrent or metastatic
             carcinoma of the breast

          -  Baseline measurements and evaluations of involved sites should be performed as close
             as possible to study entry, but must be within 4 weeks prior to randomization

          -  Patients with available tissue blocks from either the primary or metastatic site must
             submit the tissue for EGFR analysis

          -  All patients must be postmenopausal females defined by:

               -  Prior bilateral oophorectomy or bilateral ovarian irradiation

               -  No menstrual period for 12 months or longer. If age 55 years or less and on
                  tamoxifen within the prior 6 months, must have an estradiol level in the
                  postmenopausal range

          -  Patients must not have had more than 2 prior chemotherapy regimens for metastatic
             disease and no chemotherapy within 3 weeks prior to randomization; no concurrent
             chemotherapy is allowed while on protocol therapy

          -  Patients must not have prior hormonal therapy for metastatic disease; no prior therapy
             in the adjuvant setting with an estrogen receptor down-regulator (e.g. fulvestrant) or
             an aromatase inhibitor (e.g. anastrozole, letrozole, exemestane, aminoglutethamide);
             non-protocol concurrent hormonal therapy is not allowed

          -  Patients must not have had prior therapy with agents that target EGFR

          -  Previous, but not concomitant, therapy with trastuzumab (Herceptin) is allowed;
             patients must not receive trastuzumab (Herceptin) within 3 weeks prior to
             randomization

          -  Patients must have ECOG performance status of 0, 1, or 2

          -  Neutrophils >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Bilirubin =< 1.25 x upper limit of normal

          -  SGPT (ALT) and SGOT (AST) =< 2.5 x upper limit of normal if no demonstrable liver
             metastases or =< 5 times upper limit of normal in the presence of liver metastases

          -  Calculated creatinine clearance >= 30ml/min

          -  INR, PT and PTT within normal range

          -  Patients must not be receiving therapy with anticoagulants or have other
             contraindication to i.m. injections

          -  Patients must not have a history of central nervous system metastasis

          -  Patients may receive concurrent radiation therapy to painful sites of boney disease or
             areas of impending fracture as long as the radiation therapy is initiated prior to
             study entry and sites of measurable disease outside the radiation therapy port are
             available to follow; patient who have received prior radiation therapy must have
             recovered from toxicity of the prior radiation therapy

          -  Patients must not take the following medications that may alter ZD1839
             pharmacokinetics while enrolled in this trial: phenytoin, carbamazapine,
             phenobarbitol, rifampicin, and St. John's Wort, oxcarbazepine, rifapentine, modafinil,
             and griseofulvin

          -  Patients age =< 55 years must not be receiving LHRH agonists or antagonists within 3
             months prior to randomization

          -  Patients who have an ocular inflammation or infection should be fully treated before
             entry into the trial; patients with a neuropathic keratopathy or diabetes or those
             with anterior basement membrane disease must be advised of the need for frequent
             opthalmalogic exams

          -  Patients who continue to wear contact lenses must be advised that they have an
             increased risk of ocular events; the decision to wear contact lenses should be
             discussed with the patient's treating oncologist and ophthalmologist

          -  Patients must not suffer from medical or psychiatric conditions that would interfere
             with protocol compliance, the ability to provide informed consent, or assessment of
             response or anticipated toxicities

          -  Patients must be disease-free of prior invasive malignancies for > 5 years with the
             exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix