An open-label, multi-center, expanded access study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who have progressed following prior endocrine therapy, investigating the treatment of everolimus (RAD001) in combination with exemestane
- Conditions
- breast cancer10006291
- Registration Number
- NL-OMON37575
- Lead Sponsor
- ovartis Pharma BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 180
1.Adult women (* 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. ;2.Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer;3.Postmenopausal women. Postmenopausal status is defined either by:;*Age * 55 years and one year or more of amenorrhea;*Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml ;*Surgical menopause with bilateral oophorectomy ;Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression. ;4.Disease refractory to NSAI, defined as: ;a. Recurrence while on or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or;b. Progression while on or within one month of end of letrozole or anastrozole treatment for advanced BC ;5.Adequate bone marrow and coagulation function as shown by:;*Absolute neutrophil count (ANC) * 1.5 109/L;*Platelets * 100 ×109/L;*Hemoglobin (Hgb) * 9.0 g/dL;*INR * 2 ;6.Adequate liver function as shown by:;*Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) * 2.5 ULN (or * 5 if hepatic metastases are present);*Total serum bilirubin * 1.5 × ULN (* 3 × ULN for patients known to have Gilbert Syndrome) ;7.Adequate renal function as shown by:;*Serum creatinine * 1.5 × ULN;8.Fasting serum cholesterol * 300 mg/dl or 7.75 mmol/L and fasting triglycerides * 2.5 × ULN
1.HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).;2.Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting providing patient remained disease-free for at least one year following completion.;3.Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).;4.Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below: ;Topical applications, inhaled sprays, eye drops or local injections are allowed. ;Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases .;5.Bilateral diffuse lymphangitic carcinomatosis or metastasis of the lung as the only manifestation of disease (>50% of lung involvement), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan.;6.Patients with a known history of HIV seropositivity. ;7.Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is * 2.0);8.Any severe and / or uncontrolled medical conditions such as:;*Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN;*Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy;*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. ;9.Patients who test positive for hepatitis B or C (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The number and percentage of patients having any adverse events (CTCAE, version<br /><br>4.03).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Number and percentage of patients having any drug-related adverse events that<br /><br>is recorded as Grade 3 or 4 or as serious adverse event. 2: The number and<br /><br>percentage of patients having any adverse events related to concomitant<br /><br>treatment with zoledronic acid RTU formulation.</p><br>