A phase 2, double-blind, randomized, placebo-controlled, multi-center study assessing the value of adding RAD001 to letrozole (Femara®) as preoperative therapy of primary breast cancer in postmenopausal women - N/A
- Conditions
- Systemic treatment for breast cancer given when the primary tumors are still present in situ within the breast can result in large tumors being down-staged, which can allow for more conservative surgery. Letrozole (Femara) has shown to be superior to tamoxifen in this setting but with scope left for improvement. This study will investigate the additive effect that RAD001 (everolimus), can bring to therapy with letrozole in this setting.
- Registration Number
- EUCTR2004-000701-21-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 385
• Adult female patients (=18 years old)
• Histologically-confirmed diagnosis of invasive breast cancer, previously untreated (patients who have been treated for cancer of the contralateral breast can be included if there is at least a 2 year time interval from last systemic treatment for breast cancer before randomization into this study)
• Patients must be postmenopausal as defined by any of the following criteria:
1. Radiation induced menopause or surgical bilateral oophorectomy
2. Women with an intact uterus and = 55 years of age or < 55 years of age without menses for the last 5 years or < 55 years of age and has not had menses for at least the last 12 months (but has had menses in the last 5 years) and has postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives)
3. Women without an intact uterus and = 55 years of age or < 55 years of age and postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives)
• Candidates for mastectomy or breast-conserving surgery
• Primary tumor of above 2 cm diameter, measured by imaging
• Primary tumor is palpable
• Primary tumor is ER positive, defined as: = 10% of the nuclei in the invasive component of the tumor stain positive after immunostaining (analyzed in local laboratory)
• Clinical Stage M0 (bone scan, chest X-ray and abdominal CT scan or liver ultrasound required at screening to exclude metastatic disease)
• WHO performance status = 1
• Adequate bone marrow function as shown by: WBC =3.5 x 109/L, ANC = 1.5 x 109/L, Platelets = LLN, Hb >10g/dL
• Adequate liver function as shown by: serum bilirubin = 1.5 x ULN, albumin = 3 g/dl, serum transaminases activity = 2.5 x ULN, alkaline phosphatase = 2.5 x ULN
• Normal renal function (serum creatinine = 1.5 x ULN, BUN = 1.5 x ULN)
• Signed consent to participate in the study must be obtained from patients after they have been fully informed on the nature and potential risks by the investigator with the aid of written information.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
• Patients with multicentric invasive tumors (defined as additional foci of tumor outside the breast quadrant containing the primary tumor)
• Patients with bilateral or inflammatory breast cancer (a bilateral mammography is required at screening visit)
• Patients receiving concomitant anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers (BRMs), endocrine therapy (including steroids), and radiotherapy. Patients who have received hormone replacement therapy will NOT be excluded, provided that HRT is discontinued at least 2 weeks prior to entry into the study (i.e. 2 weeks prior to screening assessments).
• known hypersensitivity to everolimus or sirolimus (rapamycin), to letrozole or lactose (contained in formulations of RAD001 and letrozole)
• = grade 3 hypercholesterolemia/ hypertriglyceridemia or = grade 2 hypercholesterolemia/ hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given)
• Patients with an uncontrolled infection
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including:
- uncontrolled diabetes mellitus (fasting serum glucose > 120 mg/dL, 6.7 mmol/l),
- uncontrolled cardiac disease (unstable angina), uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration)
• Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Patients with a history of noncompliance to medical regimens
• Patients unwilling or unable to comply with the protocol (especially: 15-day biopsy, necessity to undergo breast surgery despite a clinical complete response)
• Patients who received any other investigational drugs within the 30 days prior to the screening visit
• Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method