Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: the Greko II study (GETHI2013-01).
Jesus Garcia-Donas, Laia Garrigos, Nuria Lainez, Ana Santaballa, Andres Redondo, Juan Fernando Cueva, Mª Jesus Rubio, Mario Prieto, Jose Antonio Lopez-Guerrero, Zaida Garcia-Casado, Aranzanzu Barquin, Enrique Grande, Eva Guerra Alia, Elena Sevillano, Isabel Bover, Tatiana P Grazioso, Ramón Sanchez-Escribano, Alicia Hurtado, Paloma Navarro, Juan Francisco Rodriguez-Moreno
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引用次数: 0
Abstract
Background: Granulosa cell ovarian tumors (GCTs) are a rare neoplasia characterized by a pathognomonic mutation in the FOXL2 gene. In vitro studies have demonstrated an overactivation of hormone activity due to this alteration. Thus, we aimed to determine the activity of orteronel, a CYP17 inhibitor, in advanced disease.
Methods: We designed a multicentric open-label phase II clinical trial. Eligible patients were adult woman with advanced or unresectable GCTs. Primary objective was clinical benefit rate, defined as the average of patients with radiological response plus stable disease longer than 6 months.
Results: From October 1, 2014 to May 20, 2016, ten patients were included in six participating institutions members of the GETTHI group. The study was terminated early due to a low recruitment rate. Up to 40% (CI 95% [9.6-70.4%]) cases presented a disease stabilization longer than 6 months and two of them, longer than 12 months. One patient continued on treatment at database closure 29 months after inclusion in the trial. No patient reached partial or complete response by RECIST criteria on the independent radiological review. The drug was well tolerated with nausea as the only grade 3 adverse event in one case.
Conclusion: Low accrual led to an early interruption of the study. However, orteronel achieved a promising clinical benefit rate that supports further development of new hormonotherapies in this tumor.
期刊介绍：
Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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