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.
Conditions
Interventions
Product Name: RAD001
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: Everolimus
Concentrat
Sponsors
Novartis Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 • 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
Exclusion criteria
Exclusion criteria: • Patients with multifocal invasive tumors • 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 (i.e., uncontrolled diabetes mellitus, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • the added efficacy obtained by the association of RAD001 with letrozole as preoperative therapy of primary, hormone-receptor positive breast cancer in postmenopausal women as shown by increased clinical tumor response rates • the pretreatment molecular characteristics of tumor or their modifications early in the treatment as being predictive of clinical tumor response. ;Secondary Objective: To compare the safety and tolerability of the treatment regimens. To investigate whether a reduction in tumor volume is correlated to changes in biological marker expression. To compare the number of patients that have breast-conserving surgery rather than mastectomy in the two groups after 4 months of treatment. To compare the frequency of complete pathological response achieved in the two groups after 4 months of treatment. To investigate whether co-administration of RAD001 10mg/day with letrozole 2.5 mg/day does influence letrozole pharmacokinetics and whether exposure to RAD001 is altered in the presence of letrozole, compared to historical exposure data. To investigate tumor-specific mutations and compare gene expression changes in tumor cells with blood cells and plasma for biomarker development. To investigate whether the genetic characteristics inherent to the individual are predictive of response to treatment, susceptibility to adverse events or drug-drug interactions.;Primary end point(s): Clinical tumour response rate | — |
Countries
Austria, Germany, Italy, Spain, United Kingdom
Outcome results
None listed