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Clinical Trial
. 2025 Jul;27(7):3223-3231.
doi: 10.1007/s12094-024-03827-4. Epub 2024 Dec 30.

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  1 , Laia Garrigos  2 , Nuria Lainez  3 , Ana Santaballa  4 , Andres Redondo  5 , Juan Fernando Cueva  6 , Mª Jesus Rubio  7 , Mario Prieto  8 , Jose Antonio Lopez-Guerrero  9 , Zaida Garcia-Casado  9 , Aranzanzu Barquin  10 , Enrique Grande  11 , Eva Guerra Alia  12 , Elena Sevillano  10 , Isabel Bover  13 , Tatiana P Grazioso  10 , Ramón Sanchez-Escribano  14 , Alicia Hurtado  15 , Paloma Navarro  10 , Juan Francisco Rodriguez-Moreno  10
Affiliations
Clinical Trial

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 et al. Clin Transl Oncol. 2025 Jul.

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.

Gov identifier: NCT02101684.

Keywords: Clinical trial; Granulosa cell ovarian tumors; Greko; Orteronel.

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Conflict of interest statement

Declarations. Conflict of interest: Jesus Garcia-Donas, corresponding author, has received research funding from Gilead Inc, Pfizer Inc, Merck Inc, Bristol-Myers Squibb, AstraZeneca, Novartis, MSD Inc, Roche Inc, Astellas Inc, Novartis Inc, and Exelixis Inc. He has acted as a speaker for Gilead Inc, Pfizer Inc, Merck Inc, Bristol-Myers Squibb, AstraZeneca, Novartis, Glaxo Smithkline Inc, and MSD Inc. He has served as a scientific advisor for Pfizer Inc, Merck Inc, Bristol-Myers Squibb, AstraZeneca, Novartis, and MSD Inc. Enrique Grande has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Adacap, AMGEN, Angelini, Astellas, Astra Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho, and Thermo Fisher Scientific. EG has received research grants from Pfizer, Astra Zeneca, Astellas, and Lexicon Pharmaceuticals. AR has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Astellas, Bristol Myers Squibb, IPSEN, Pfizer, and MSD. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: All participants provided informed consent prior to their participation.

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