Phase II Study of Everolimus Beyond Progression
Condition: Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: everolimus; anastrozole; letrozole; tamoxifen citrate; fulvestrant; megestrol acetate
Intervention description: Given PO; Given PO; Given PO; Given PO; Given IM or PO; Given PO
Intervention MeSH terms: Tamoxifen; Everolimus; Letrozole; Fulvestrant; Anastrozole; Megestrol; Megestrol Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well everolimus and hormone therapy work in treating patients
      with hormone receptor positive breast cancer that has continued to spread (progressed) or
      returned after a period of improvement (recurred) on everolimus and exemestane hormone
      therapy. Everolimus is a chemotherapy drug that may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. Estrogen and progesterone are hormones
      that can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by
      lowering the amount of estrogen and progesterone the body makes. Giving everolimus with a
      different type of hormone therapy may be an effective treatment for breast cancer in patients
      who progressed on everolimus with exemestane.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Estrogen (ER) and/or progesterone (PR)-positive at primary diagnosis and at metastatic
             diagnosis where tissue is available (defined as > or = 1% of staining nuclei)

          -  Progressive or recurrent breast cancer defined as disease progression or recurrence
             while on a combination of exemestane with everolimus

          -  Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard
             criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]
             negative if IHC 2+) at primary diagnosis

          -  Histologically confirmed, measurable or evaluable disease; patients should have at
             least one measurable lesion; if applicable, Response Evaluation Criteria in Solid
             Tumors (RECIST) criteria should be used

          -  Life expectancy > 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Absolute neutrophil count (ANC) > 1,500/µL

          -  Platelets ≥ 100,000/µL

          -  Hemoglobin > 10 g/dL

          -  Creatinine ≤ 1.5 x upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 x ULN

          -  International normalized ratio ≤ 1.3 (or ≤ 3 on anticoagulants)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x ULN unless
             related to primary disease

          -  Signed informed consent

          -  Adequate birth control

          -  Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5
             x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can
             only be included after initiation of appropriate lipid lowering medication

        Exclusion Criteria:

          -  Prior treatment with everolimus other than in combination with hormonal therapy for
             treatment of breast cancer or prior treatment with another mammalian target of
             rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indication

          -  HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and
             metastatic sites)

          -  Active infection: temperature > 100 Fahrenheit (F), fever of unknown origin, active
             symptoms or signs of infection as defined by the investigator

          -  Uncontrolled central nervous system metastases

          -  Life-threatening, visceral metastases

          -  Pregnant or lactating women

          -  Prior chemotherapy within the last 4 weeks

          -  Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator
             lesion (unless objective disease recurrence or progression within the radiation portal
             has been documented since completion of radiation)

          -  Concomitant malignancies or previous malignancies within the last 5 years, with the
             exception of adequately treated basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix

          -  History of significant cardiac disease, cardiac risk factors or uncontrolled
             arrhythmias

          -  Hypersensitivity to trial medications (everolimus)

          -  Emotional limitations, which the investigator judges could limit the patient's ability
             to follow up and comply with study procedures

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent

          -  Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN

          -  Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
             hepatitis

          -  A known history of human immunodeficiency virus (HIV) seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of EVEROLIMUS (e.g., ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
             resection)

          -  Patients with an active, bleeding diathesis

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods; if barrier contraceptives
             are being used, these must be continued throughout the trial by both sexes; hormonal
             contraceptives are not acceptable as a sole method of contraception; (women of
             childbearing potential must have a negative urine or serum pregnancy test within 7
             days prior to administration of EVEROLIMUS)

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs,
             resulting in dyspnea at rest

          -  Taking any of the following agents:

               -  Chronic treatment with systemic steroids or another immunosuppressive agent (use
                  of steroids as part of management of everolimus toxicities will be allowed)

               -  Live vaccines

               -  Patients who have received live attenuated vaccines within 1 week of start of
                  everolimus and during the study; patient should also avoid close contact with
                  others who have received live attenuated vaccines; examples of live attenuated
                  vaccines include intranasal influenza, measles, mumps, rubella, oral polio,
                  bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid
                  vaccines

               -  Drugs or substances known to be inhibitors or inducers of the isoenzyme
                  cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A)