Open Label Phase Ii Clinical Trial Of Orteronel (Tak-700) In Metastatic Or Advanced Non-Resectable Granulosa Cell Ovarian Tumors: The Greko Ii Study.

TPS2598Background: Granulosa-cell tumors (GCT) of the ovary are a rare entity characterized by a pathognomonic punctual mutation at the FOXL2 gene 402C→G (C134W). This alteration leads to an upregulaton of the enzyme CYP17 (key in androgens and 17-OH-progesterone synthesis). Interestingly, a previous study by our group has demonstrated clinical activity of ketoconazole, a well known CYP17 inhibitor (GREKO I trial). Additionally, cell cultures of both adult and juvenlie GCT showed an increased sensitivity to both ketoconazole and abiraterone compare to pancreatic tumors and lung adenocarcinoma. Orteronel (TAK700) is a selective inhibitor of 17, 20-lyase, that is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Thus we aimed to test the clinical activity of such drug in GCT. Methods: An open-label phase II single arm clini...