Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)

Inclusion Criteria: * Histologically confirmed diagnosis of adrenocortical carcinoma * Locally advanced or metastatic disease not amenable to radical surgery resection (Stage III-IV) * Radiologically monitorable disease * ECOG performance status 0-2 * Life expectancy \> 3 months * Age ≥18 years * Adequate bone marrow reserve (neutrophils \> 1500/mm3 and platelets \> 100,000/mm3) * Effective contraception in pre-menopausal female and male patients * Patient's written informed consent * Ability to comply with the protocol procedures (including availability for follow-up visits) * Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiable afterwards. Exclusion Criteria: * History of prior malignancy, except for cured non-melanoma skin cancer, curatively in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years. * Previous cytotoxic chemotherapy for adrenocortical carcinoma * Renal insufficiency (serum creatinine ≥2 mg/dl or creatinine clearance ≤ 50 ml/min) * Hepatic insufficiency (serum bilirubin ≥2 x the institutional upper limit of normal range and/or serum transaminases ≥ 3 x the institutional upper limit of normal range; exception: in patients on mitotane, transaminase levels up to 5 x the institutional upper limit of normal range are acceptable) * Pregnancy or breast feeding * Known hypersensitivity to any drug included in the treatment prot…