Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Everolimus; Fulvestrant
Intervention description: Everolimus tablets, two-5 mg tablets a day; intramuscular, 500 mg in two divided doses- one on each side- on day 1, then 250mg on day 14, then 250 mg on day 28 and every 4 weeks +/- 3 days thereafter
Intervention MeSH terms: Everolimus; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Breast cancer; Fulvestrant; Everolimus

Summary:

      The primary objective of this study is to determine if estrogen receptor-targeted therapy
      with fulvestrant used in combination with Everolimus is an effective and safe therapy for
      women with hormone receptor positive metastatic breast cancer after failure of aromatase
      inhibitor therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal status, defined as any one of the following criteria: Documented
             history of bilateral oophorectomy, Age 60 years or more, OR Age 45 to 59 and
             satisfying one or more of the following criteria: Amenorrhea for at least 12 months
             and intact uterus OR Amenorrhea for less than 12 months and a follicle stimulating
             hormone (FSH) concentration - within postmenopausal range including: Patients who have
             had a hysterectomy or Patients who have received hormone replacement

          -  Patients must have histologically confirmed invasive breast cancer

          -  Metastatic or locally advanced disease

          -  Patients must have estrogen receptor and/or progesterone receptor positive disease

          -  Measurable or evaluable disease

          -  Failure of aromatase inhibitor therapy within the previous 6 months. Patients who
             received prior tamoxifen are eligible to enroll

          -  Prior aromatase inhibitor therapy or other endocrine therapy must be discontinued at
             least 1 week prior to enrollment and any toxicity from such therapy must have reverted
             to grade I or less at the time of enrollment

          -  Patients must not have received chemotherapy, radiation therapy, or had surgery within
             4 weeks prior to enrollment and any toxicity from such therapy must have recovered to
             grade 1 or less prior to enrollment

          -  Patients must not have received either of the study medications previously

          -  WHO performance status of 0, 1, or 2

          -  Adequate organ function defined as follows: Adequate renal function, defined by a
             serum creatinine within the upper limits of normal, Adequate liver function, defined
             by a bilirubin of < 1.5 the upper limit of normal (ULN) and aspartate aminotransferase
             (AST), alanine aminotransferase (ALT) of ≤ 2.5 times the ULN, Adequate bone marrow
             function, defined as an absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count
             (PLT) >100,000/ul, Hb >9 gm/dl, international normalized ratio (INR) <1.3, and because
             fulvestrant is administered intramuscularly, it should not be used in patients with
             bleeding diatheses, thrombocytopenia or in patients on anticoagulants

          -  Patients will be asked to provide a tumor paraffin block if available

          -  Ability to understand and sign a written informed consent for participation in the
             trial

        Exclusion Criteria:

          -  Known severe hypersensitivity to everolimus (or similar drugs) or any of the
             excipients of this product

          -  Premenopausal status

          -  Other coexisting malignancies with the exception of basal cell carcinoma or cervical
             cancer in situ

          -  Patients with brain metastasis or leptomeningeal involvement

          -  Patients with malignant pleural effusion or ascites only disease

          -  Rapidly progressive visceral disease

          -  WHO performance status of 3 or 4

          -  As judged by the investigator, uncontrolled intercurrent illness including, but not
             limited to: Ongoing or active infection, Symptomatic congestive heart failure,
             Unstable angina pectoris or significant cardiac arrhythmia, Psychiatric illness/social
             situations that would limit compliance with study requirements, Severely impaired lung
             function such as severe chronic obstructive pulmonary disease (COPD) or interstitial
             lung disease, a known forced expiratory volume at one second (FEV1) of < 1.5 liters,
             or dyspnea of grade III or greater, Uncontrolled diabetes as defined by a fasting
             blood sugar (FBS) of > 1.5 ULM, Known liver disease such as cirrhosis or chronic
             hepatitis, Known HIV positivity, OR known condition causing malabsorption

          -  Chronic treatment with systemic steroids or other immunosuppressive agents

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Evidence of any other significant clinical disorder or laboratory finding that makes
             it undesirable for the subject to participate in the clinical trial

          -  Prior treatment with an mTOR inhibitor

          -  Treatment with a non-approved or investigational drug within 30 days or 5 half-lives
             of the drug, whichever is greater, before Day 1 of study treatment

          -  In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that
             would preclude intramuscular injections

          -  History of hypersensitivity to castor oil