An Open Label Study of Postmenopausal Women With Oestrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) With Exemestane, With Exploratory Epigenetic Marker Analysis

Exclusion Criteria

• •HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• •Pre-menopausal, pregnant, lactating women.
• •Known hypersensitivity to mammilian target of Rapamycin (mTOR) inhibitors, e.g. sirolimus (rapamycin) or to their excipients.
• •Known hypersensitivity to exemestane, to the active substance or to any of the excipients.
• •Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
• •Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
• •Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
• •Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
• •Prolonged systemic corticosteroid treatment during study, except for topical applications (e.g. rash),inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) should not be given. However:
• •short duration (\<2 weeks) of systemic corticosteroids is allowed (e.g. chronic obstructive pulmonary disease, anti-emetic)
• •low doses of corticosteroids for brain metastasis treatment is allowed
• •Patients with symptomatic visceral metastasis (e.g. significant dyspnoea related to pulmonary lymphangitic carcinomatosis and lung metastases or clinically meaningful symptomatic liver metastasis)
• •Symptomatic brain or other Central Nervous system (CNS) metastases.
• •Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, low molecular weight heparin (LMWH) and acetylsalicylic acid or equivalent, as long as the INR is 2.0)
• •Any severe and / or uncontrolled medical conditions such as:
• •* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
• •* Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 × ULN
• •* Acute and chronic, active infectious disorders (except for Hep B and Hep C positive patients) and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
• •* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome)
• •* Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
• •Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) within the last 5 days prior to enrollment
• •History of non-compliance to medical regimens
• •Patients unwilling to or unable to comply with the protocol
• •Another malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer