Trial of RAD001 in Triple Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: RAD 001
Intervention description: RAD 001-10 mg by mouth once everyday
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; metastatic breast; triple negative; ER/PR negative; Her2 Neu negative

Summary:

      The hypothesis of this clinical research study is to discover if the study drug RAD001 can
      shrink or slow the growth of Estrogen Receptor/Progesterone Receptor (ER/PR) negative or
      Human Epidermal growth factor Receptor 2 (Her2 Neu) negative breast cancer. The safety of
      RAD001 will also be studied. Patients physical state, symptoms, changes in the size of the
      tumor, and laboratory findings obtained while on-study will help the research team decide if
      RAD001 is safe and effective.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eastern Cooperative Group (ECOG) performance status ≤ 2

          -  Age ≥ 18 years

          -  At least one measurable site of disease according to RECIST criteria that has not been
             previously irradiated. If the patient has had previous radiation to the marker
             lesion(s), there must be evidence of disease progression since the radiation

          -  Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) ≥ 1.5 x
             109/L, Platelets (PLT)≥ 100 x 109/L, Hemoglobin (HGB) ≥9 g/dL

          -  Adequate liver function as shown by:Serum bilirubin ≤ 1.5 x upper limits of normal
             (ULN), Prothrombin Time (INR) ≤ 1.3 (or ≤ 3 on anticoagulants), Liver function teats ≤
             2.5x ULN (≤ 5x ULN in patients with liver metastases)

          -  Adequate renal function: serum creatinine ≤ 1.5 x ULN

          -  Controlled diabetes as defined by fasting serum glucose ≤1.5 x ULN

          -  Fasting serum cholesterol ≤300 mg/dL or ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x
             ULN.

        Exclusion Criteria:

          -  Currently receiving anticancer therapies or who have received anticancer therapies
             within 4 weeks of the start of study drug (including chemotherapy, antibody based
             therapy, etc.)

          -  Palliative radiation therapy only allowed to localized areas (ie: painful rib lesion),
             at the discretion of the PI and treating radiation oncologist

          -  Major surgery/significant traumatic injury within 4 weeks of start of study drug.

          -  Not recovered from the side effects of any major surgery (defined as requiring general
             anesthesia) to Grade I or patients that may require major surgery during the course of
             the study.

          -  Prior treatment with any investigational drug within the preceding 4 weeks

          -  Receiving chronic immunosuppressive agents, except corticosteroids with a daily dosage
             equivalent to prednisone ≤ 20 milligrams (mg). However, patients receiving
             corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks
             prior to the first treatment with RAD001. Topical or inhaled corticosteroids are
             allowed.

          -  May not receive immunization with attenuated live vaccines within one week of study
             entry or during study period.

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases

          -  Other malignancies within the past 3 years, except for adequately treated carcinoma of
             the cervix and basal or squamous cell carcinomas of the skin.

          -  Severe and/or uncontrolled medical conditions or other conditions that could affect
             their participation in the study such as: Congestive heart failure: New York Heart
             Association Class III/IV, Unstable angina pectoris, symptomatic congestive heart
             failure, myocardial infarction within 6 months of start of study drug, serious
             uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.

          -  Impaired lung function (PFT screen at baseline) as defined as spirometry and DLCO that
             is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest
             on room air.

          -  Uncontrolled diabetes as defined by fasting serum glucose ≥1.5 x ULN. Glucose control
             should be achieved before starting a patient on RAD001.

          -  Active (acute or chronic) or uncontrolled severe infections

          -  Liver disease(cirrhosis, chronic active hepatitis or chronic persistent hepatitis)

          -  Known history of Human Immunodeficiency Virus (HIV) seropositivity

          -  Impairment of gastrointestinal function/disease that may significantly alter the
             absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting,
             diarrhea, malabsorption syndrome or small bowel resection)

          -  Active, bleeding diathesis

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods.

          -  Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).

          -  Known hypersensitivity to RAD001 (everolimus) or other rapamycin drugs (sirolimus,
             temsirolimus) or to its excipients