Ketoconazole As Inhibitor Of The Enzyme Cyp17 In Locally Advanced Or Disseminated Granulosa Cell Tumors Of The Ovary (The Greko I Study) (Gethi 11-03).

5558 Background: Granulosa-cell tumors (GCTs) of the ovary are a rare entity characterized by its genomic stability, presenting a punctual mutation at the FOXL2 gene, 402C→G (C134W), in the vast majority of cases. The protein encoded by this gene directly interacts with the Steroidogenic Factor-1 (SF-1) that regulates the expression of the enzyme CYP17. Since CYP17 inhibition has shown major activity in some cancers, we aimed to test the role of ketoconazole in GCT in a proof of concept trial. Methods: An open-label phase II trial was designed. Main inclusion criteria was adult women with advanced non-resectable GCT. Primary objective was radiological response, centrally assessed. Taking as a basis the two-stage Gehan model, 17 patients would need to be included in the first stage to demonstrate a treatment efficacy of at least 15% (type I error α = 0.05, power of the test (1 - β) = 0.8). Treatment consisted on oral Ketoconazole 400 mg tid plus hydrocortisone 30 mg in morning and 20 mg in evening. 10 inst...