

2 or 3 weeks from Abiraterone start), then Mitotane +/- chemotherapy can be started upon the clinician's decision. If the primary endpoint is obtained before 1 month (i.e. In this cohort, AA in association with Mitotane will be administered for 3 months. In this cohort, Mitotane and chemotherapy will be interrupted and AA will be continued till progression and/or as long as the Cushing's syndrome is adequately controlled (ie until progression of Cushing's syndrome).Ĭohort 2: Mitotane-naïve patients with newly diagnosis of ACC associated with Cushing's syndrome not amenable to surgical resection with radical intent will be treated with single agent AA for 4 weeks followed by AA + Mitotane +/- first-line chemotherapy. The study is a phase II, non-randomized, open-label study with two different experimental sub-cohorts:Ĭohort 1: Patients locally advanced/metastatic ACC patients with uncontrolled Cushing's syndrome despite Mitotane +/- chemotherapy will be treated with single agent AA. Thus, we decided to evaluate the activity of Abiraterone Acetate in the management of Cushing's syndrome in patients with adrenocortical carcinoma. AA has a pharmacodynamic potential to reduce cortisol excess and it has never been tested before in Cushing's syndrome.

Moreover, hypercortisolism is one of the factors that negatively influence the outcome of patients with metastatic ACC.Ībiraterone acetate (AA) is a prodrug of abiraterone, an irreversible inhibitor of 17α hydroxylase/C17, 20-lyase (cytochrome P450c17 ).The inhibition of CYP17A1 blocks androgen and cortisol synthesis.

Cortisol hypersecretion (Cushing's syndrome) is the most common endocrine derangement at presentation. Approximately 50% of ACC in adults are functioning leading to hormonal and metabolic syndromes. Why Should I Register and Submit Results?Īdrenocortical Carcinoma (ACC) is an extremely rare disease.
