Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer

• Phase l: To establish the feasible dose levels/regimens based on End-of-cycle-1 dose limiting toxicity rate. [ Time Frame: at every critical DLT, after 6 patients have completed cycle 1 or every 2 months ] [ Designated as safety issue: Yes ]
• Phase II: To evaluate the efficacy of the dose/level regimen of RAD001 recommended from the phase I with trastuzumab and paclitaxel therapy. This will be based on the overall response rate. [ Time Frame: every 8 - 9 weeks ] [ Designated as safety issue: No ]

• Phase I : Assess ability to deliver trastuzumab and paclitaxel therapy based on the relative dose intensity of paclitaxel & on the discontinuation rate of trastuzumab, assess everolimus, trastuzumab & paclitaxel PK in a subset of patients [ Time Frame: every 8 - 9 weeks ] [ Designated as safety issue: No ]
• To evaluate progression free survival (PFS), overall survival(OS) and to describe the safety profile of the phase II part combination. [ Time Frame: every 8 - 9 weeks and for OS, every 3 months ] [ Designated as safety issue: Yes ]

• To assess the ability to deliver the trastuzumab and paclitaxel therapy
• To assess everolimus, trastuzumab and paclitaxel blood levels in this combination
• To evaluate the overall tumor response

Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.

Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.

Inclusion Criteria:

• Female or male patients ≥ 18 years old with WHO performance status ≤ 1
• HER-2 over-expressing metastatic breast cancer cells confirmed by histology
• Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
• Patient resistance to trastuzumab and taxanes (Phase ll)
• Measurable disease according to RECIST (Phase ll)
• Patients neurologically stable with adequate bone marrow, liver and renal function

Exclusion Criteria:

• Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
• Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
• Patients who have previously received mTOR inhibitors

Other protocol-defined inclusion/exclusion criteria may apply