1. Inicio
  2. Publicaciones
  3. 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.

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.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Garcia-Donas, Jesus
  • Hurtado, Alicia
  • Garrigos, Laia
  • 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 Perez
  • Navarro, Paloma
  • Grande, Enrique
  • Spanish Group for Research in Orphan, Infrequent Tumors (GETHI)

Abstract

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). GOV IDENTIFIER: NCT01584297.

© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).

Datos de la publicación

ISSN/ISSNe:
1699-048X, 1699-3055

CLINICAL & TRANSLATIONAL ONCOLOGY  SPRINGER-VERLAG ITALIA SRL

Tipo:
Article
Páginas:
2090-2098
PubMed:
36708371
Factor de Impacto:
0,764 SCImago ℠
Cuartil:
Q2 SCImago ℠

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • Granulosa cell ovarian cancer; Hormonetherapy; Ketoconazole

Campos de Estudio

Cita

Compartir