Sorafenib and Letrozole, Anastrozole, or Exemestane in Treating Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: anastrozole; exemestane; letrozole; sorafenib tosylate; placebo
Intervention description: given orally; given orally; given orally; given orally; given orally
Intervention MeSH terms: Sorafenib; Letrozole; Anastrozole; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor
      and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of
      breast cancer cells. Aromatase inhibition therapy using letrozole, anastrozole, or exemestane
      may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet
      known whether sorafenib is more effective than a placebo when given together with letrozole,
      anastrozole, or exemestane in treating metastatic breast cancer.

      PURPOSE: This randomized phase II trial is studying how well sorafenib works compared with a
      placebo when given together with letrozole, anastrozole, or exemestane in treating
      postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive
      metastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed adenocarcinoma of the breast

               -  Metastatic disease

          -  Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
             conventional techniques (i.e., MRI or CT scan of chest, abdomen and pelvis) or ≥ 10 mm
             by spiral CT scan

               -  Non-measurable disease allowed, defined as all other lesions (or sites of
                  disease), including small lesions (longest diameter < 20 mm by conventional
                  techniques or < 10 mm by spiral CT scan)

          -  Must have objective evidence of progression within the past 3 months

          -  No human epidermal growth factor receptor 2 (HER2)/neu overexpression, defined as gene
             amplification by fluorescence in situ hybridization or 3+ overexpression by
             immunohistochemistry, or unknown HER2/neu status

          -  No active brain metastases

               -  Patients with neurological symptoms must undergo a contrast CT scan or MRI of the
                  brain to exclude active brain metastasis

               -  Patients with treated brain metastases allowed provided they have no evidence of
                  disease and have been off definitive therapy (including steroids) for the past 3
                  months

          -  Hormone receptor status:

               -  Estrogen receptor- and/or progesterone receptor-positive disease

        PATIENT CHARACTERISTICS:

          -  Female

          -  The Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Postmenopausal

          -  Hemoglobin ≥ 9.0 g/dL

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)

          -  INR ≤ 1.5

          -  PTT within normal limits

          -  Creatinine ≤ 1.5 times ULN

          -  Not nursing, pregnant, or able to become pregnant

          -  No significant traumatic injury within the past 4 weeks

          -  No history of bleeding diathesis or uncontrolled coagulopathy

          -  No serious, nonhealing wound, ulcer, or bone fracture

          -  No clinically significant cardiac disease, including any of the following:

               -  New York Heart Association class III-IV congestive heart failure

               -  Unstable angina (i.e., anginal symptoms at rest) or new-onset angina (i.e., began
                  within the past 3 months)

               -  Myocardial infarction within the past 6 months

          -  No cardiac ventricular arrhythmias requiring antiarrhythmic therapy

          -  No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg),
             despite optimal medical management

          -  No thrombolic, embolic, venous, or arterial events (e.g., cerebrovascular accident
             including transient ischemic attacks) within the past 6 months

          -  No pulmonary hemorrhage or bleeding event > grade 2 within the past 4 weeks

          -  No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks

          -  No active clinically serious infection > grade 2

          -  No known HIV infection

          -  No chronic hepatitis B or C infection

          -  No previous or concurrent cancer that is distinct in primary site or histology from
             breast cancer except carcinoma in situ of the cervix, treated basal cell skin cancer,
             superficial bladder tumors (i.e., Ta and Tis), or any cancer curatively treated within
             the past 5 years

          -  No known or suspected allergy to sorafenib tosylate or other agents used in this study

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No major surgery or open biopsy within the past 4 weeks

          -  No more than 1 prior regimen of endocrine therapy for metastatic breast cancer,
             provided that the patient has not received an aromatase inhibitor within the past 12
             months

          -  No more than 1 prior regimen of chemotherapy for metastatic disease

          -  More than 2 weeks since prior radiotherapy, except if to a non-target lesion only or
             single-dose radiotherapy for palliation

               -  Prior radiotherapy to a target lesion(s) is permitted only if there has been
                  clear progression of the lesion since radiotherapy was completed

          -  Concurrent anticoagulation treatment (e.g., warfarin or heparin) allowed

          -  No concurrent Hypericum perforatum (St. John's wort), rifampin, bevacizumab, or any
             other drugs (licensed or investigational) that target vascular endothelial growth
             factor (VEGF) or VEGF receptors

          -  No concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs (e.g., phenytoin,
             carbamazepine, or phenobarbital)