ELBA: Exemestane and Lapatinib in Advanced Breast Cancer

• Histological diagnosis of breast cancer
• Indication for hormonal therapy (ER and/or PgR positive)
• Stage IV disease
• Female gender
• Postmenopausal status (patients treated with LHRH analogs are eligible for the Phase II part of the study)
• At least one target or non-target lesion according to RECIST criteria
• ECOG Performance Status 0-2
• Adequate bone marrow (neutrophils > or = 1.500/mm³, platelets > or = 100.000/mm³ and hemoglobin > or = 9 g/dl), hepatic (GOT, GPT \< 2.5 e bilirubin \<1.25 times the value of upper normal limit) and renal (creatinine \< 1.25 times the value of upper normal limit) function
• Adequate cardiac function (FEVS > or = 50%)
• Able to take oral medications
• Life expectancy > 3 months
• Signed informed consent

Exclusion Criteria:

• Any previous hormone therapy for metastatic disease
• More than one line of chemotherapy for metastatic disease (first line chemotherapy is permitted)
• Symptomatic cerebral metastases
• Planned concomitant radiation therapy in the first month of therapy (for those patients participating in the dose finding phase of the study)
• Previous therapy with exemestane, including as adjuvant therapy (previous therapy with non-steroidal aromatase inhibitors is permitted)
• Previous or concurrent malignancy in past 5 years (excluding adequately treated basal cel or spinocellular skin cancer and in situ carcinoma of the cervix)
• Treatment with experimental pharmacologic therapy within 4 weeks of enrollment in the study
• Unable or unwilling to provide signed informed consent
• Any concurrent illness that would, in the Investigator's opinion, contraindicate the use of the study drugs.
• Active infection
• Assumption of CYP3A4 inhibitors or inducers (ketoconazole, itraconazole, fluconazole, macrolide antibiotics, antidepressives, calcium-antagonists, cimetidine, carbamazepine, phenytoin, barbiturates, rifampicin e glucocorticoids)
• Pregnancy or lactation
• Unable to comply with follow-up
• Active hepatobiliary disease (with the exception of Gilbert's syndrome, asymptomatic biliary calculi, hepatic metastases or stabile chronic hepatopathy)