Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03
Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to...
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| Autor*in: |
Garcia-Donas, Jesus [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
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2023 |
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© The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Revista de oncología - Barcelona : Doyma, 2000, 25(2023), 7 vom: 28. Jan., Seite 2090-2098 |
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| Übergeordnetes Werk: |
volume:25 ; year:2023 ; number:7 ; day:28 ; month:01 ; pages:2090-2098 |
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| DOI / URN: |
10.1007/s12094-023-03085-w |
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SPR051839040 |
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| 245 | 1 | 0 | |a Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 |
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| 520 | |a Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. | ||
| 650 | 4 | |a Granulosa cell ovarian cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Ketoconazole |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Hurtado, Alicia |4 aut | |
| 700 | 1 | |a Garrigos, Laia |4 aut | |
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| 700 | 1 | |a Rodriguez, Victor |4 aut | |
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| 700 | 1 | |a Bover, Isabel |4 aut | |
| 700 | 1 | |a Palacio, Isabel |4 aut | |
| 700 | 1 | |a Rubio, Maria Jesus |4 aut | |
| 700 | 1 | |a Prieto, Mario |4 aut | |
| 700 | 1 | |a Lopez-Guerrero, Jose Antonio |4 aut | |
| 700 | 1 | |a Rodriguez-Moreno, Juan Francisco |4 aut | |
| 700 | 1 | |a Garcia-Casado, Zaida |4 aut | |
| 700 | 1 | |a Garcia-Martinez, Elena |4 aut | |
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| 700 | 1 | |a de Castro, Ignacio Pérez |4 aut | |
| 700 | 1 | |a Navarro, Paloma |4 aut | |
| 700 | 1 | |a Grande, Enrique |4 aut | |
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10.1007/s12094-023-03085-w doi (DE-627)SPR051839040 (SPR)s12094-023-03085-w-e DE-627 ger DE-627 rakwb eng Garcia-Donas, Jesus verfasserin (orcid)0000-0001-7731-3601 aut Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. Granulosa cell ovarian cancer (dpeaa)DE-He213 Ketoconazole (dpeaa)DE-He213 Hormonetherapy (dpeaa)DE-He213 Hurtado, Alicia aut Garrigos, Laia aut Santaballa, Ana aut Redondo, Andres aut Vidal, Laura aut Lainez, Nuria aut Guerra, Eva aut Rodriguez, Victor aut Cueva, Juan aut Bover, Isabel aut Palacio, Isabel aut Rubio, Maria Jesus aut Prieto, Mario aut Lopez-Guerrero, Jose Antonio aut Rodriguez-Moreno, Juan Francisco aut Garcia-Casado, Zaida aut Garcia-Martinez, Elena aut Taus, Alvaro aut de Castro, Ignacio Pérez aut Navarro, Paloma aut Grande, Enrique aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 28. Jan., Seite 2090-2098 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:28 month:01 pages:2090-2098 https://dx.doi.org/10.1007/s12094-023-03085-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 28 01 2090-2098 |
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10.1007/s12094-023-03085-w doi (DE-627)SPR051839040 (SPR)s12094-023-03085-w-e DE-627 ger DE-627 rakwb eng Garcia-Donas, Jesus verfasserin (orcid)0000-0001-7731-3601 aut Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. Granulosa cell ovarian cancer (dpeaa)DE-He213 Ketoconazole (dpeaa)DE-He213 Hormonetherapy (dpeaa)DE-He213 Hurtado, Alicia aut Garrigos, Laia aut Santaballa, Ana aut Redondo, Andres aut Vidal, Laura aut Lainez, Nuria aut Guerra, Eva aut Rodriguez, Victor aut Cueva, Juan aut Bover, Isabel aut Palacio, Isabel aut Rubio, Maria Jesus aut Prieto, Mario aut Lopez-Guerrero, Jose Antonio aut Rodriguez-Moreno, Juan Francisco aut Garcia-Casado, Zaida aut Garcia-Martinez, Elena aut Taus, Alvaro aut de Castro, Ignacio Pérez aut Navarro, Paloma aut Grande, Enrique aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 28. Jan., Seite 2090-2098 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:28 month:01 pages:2090-2098 https://dx.doi.org/10.1007/s12094-023-03085-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 28 01 2090-2098 |
| allfields_unstemmed |
10.1007/s12094-023-03085-w doi (DE-627)SPR051839040 (SPR)s12094-023-03085-w-e DE-627 ger DE-627 rakwb eng Garcia-Donas, Jesus verfasserin (orcid)0000-0001-7731-3601 aut Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. Granulosa cell ovarian cancer (dpeaa)DE-He213 Ketoconazole (dpeaa)DE-He213 Hormonetherapy (dpeaa)DE-He213 Hurtado, Alicia aut Garrigos, Laia aut Santaballa, Ana aut Redondo, Andres aut Vidal, Laura aut Lainez, Nuria aut Guerra, Eva aut Rodriguez, Victor aut Cueva, Juan aut Bover, Isabel aut Palacio, Isabel aut Rubio, Maria Jesus aut Prieto, Mario aut Lopez-Guerrero, Jose Antonio aut Rodriguez-Moreno, Juan Francisco aut Garcia-Casado, Zaida aut Garcia-Martinez, Elena aut Taus, Alvaro aut de Castro, Ignacio Pérez aut Navarro, Paloma aut Grande, Enrique aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 28. Jan., Seite 2090-2098 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:28 month:01 pages:2090-2098 https://dx.doi.org/10.1007/s12094-023-03085-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 28 01 2090-2098 |
| allfieldsGer |
10.1007/s12094-023-03085-w doi (DE-627)SPR051839040 (SPR)s12094-023-03085-w-e DE-627 ger DE-627 rakwb eng Garcia-Donas, Jesus verfasserin (orcid)0000-0001-7731-3601 aut Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. Granulosa cell ovarian cancer (dpeaa)DE-He213 Ketoconazole (dpeaa)DE-He213 Hormonetherapy (dpeaa)DE-He213 Hurtado, Alicia aut Garrigos, Laia aut Santaballa, Ana aut Redondo, Andres aut Vidal, Laura aut Lainez, Nuria aut Guerra, Eva aut Rodriguez, Victor aut Cueva, Juan aut Bover, Isabel aut Palacio, Isabel aut Rubio, Maria Jesus aut Prieto, Mario aut Lopez-Guerrero, Jose Antonio aut Rodriguez-Moreno, Juan Francisco aut Garcia-Casado, Zaida aut Garcia-Martinez, Elena aut Taus, Alvaro aut de Castro, Ignacio Pérez aut Navarro, Paloma aut Grande, Enrique aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 28. Jan., Seite 2090-2098 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:28 month:01 pages:2090-2098 https://dx.doi.org/10.1007/s12094-023-03085-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 28 01 2090-2098 |
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10.1007/s12094-023-03085-w doi (DE-627)SPR051839040 (SPR)s12094-023-03085-w-e DE-627 ger DE-627 rakwb eng Garcia-Donas, Jesus verfasserin (orcid)0000-0001-7731-3601 aut Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. Granulosa cell ovarian cancer (dpeaa)DE-He213 Ketoconazole (dpeaa)DE-He213 Hormonetherapy (dpeaa)DE-He213 Hurtado, Alicia aut Garrigos, Laia aut Santaballa, Ana aut Redondo, Andres aut Vidal, Laura aut Lainez, Nuria aut Guerra, Eva aut Rodriguez, Victor aut Cueva, Juan aut Bover, Isabel aut Palacio, Isabel aut Rubio, Maria Jesus aut Prieto, Mario aut Lopez-Guerrero, Jose Antonio aut Rodriguez-Moreno, Juan Francisco aut Garcia-Casado, Zaida aut Garcia-Martinez, Elena aut Taus, Alvaro aut de Castro, Ignacio Pérez aut Navarro, Paloma aut Grande, Enrique aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 28. Jan., Seite 2090-2098 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:28 month:01 pages:2090-2098 https://dx.doi.org/10.1007/s12094-023-03085-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 28 01 2090-2098 |
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Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 |
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Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). ClinicalTrials.gov Identifier NCT01584297. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03 |
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Hurtado, Alicia Garrigos, Laia Santaballa, Ana Redondo, Andres Vidal, Laura Lainez, Nuria Guerra, Eva Rodriguez, Victor Cueva, Juan Bover, Isabel Palacio, Isabel Rubio, Maria Jesus Prieto, Mario Lopez-Guerrero, Jose Antonio Rodriguez-Moreno, Juan Francisco Garcia-Casado, Zaida Garcia-Martinez, Elena Taus, Alvaro de Castro, Ignacio Pérez Navarro, Paloma Grande, Enrique |
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Hurtado, Alicia Garrigos, Laia Santaballa, Ana Redondo, Andres Vidal, Laura Lainez, Nuria Guerra, Eva Rodriguez, Victor Cueva, Juan Bover, Isabel Palacio, Isabel Rubio, Maria Jesus Prieto, Mario Lopez-Guerrero, Jose Antonio Rodriguez-Moreno, Juan Francisco Garcia-Casado, Zaida Garcia-Martinez, Elena Taus, Alvaro de Castro, Ignacio Pérez Navarro, Paloma Grande, Enrique |
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