Garcia-Donas Jesus, Garrigos Laia, Lainez Nuria, Santaballa Ana, Redondo Andres, Cueva Juan Fernando, Rubio Mª Jesus, Prieto Mario, Lopez-Guerrero Jose Antonio, Garcia-Casado Zaida, Barquin Aranzanzu, Grande Enrique, Alia Eva Guerra, Sevillano Elena, Bover Isabel, Grazioso Tatiana P, Sanchez-Escribano Ramón, Hurtado Alicia, Navarro Paloma, Rodriguez-Moreno Juan Francisco
HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Laboratorio de Innovación en Oncología, Instituto de Investigación Sanitaria HM Hospitales, Oña Street 10, 28050, Madrid, Spain.
Hospital del Mar, Barcelona, Spain.
Clin Transl Oncol. 2024 Dec 30. doi: 10.1007/s12094-024-03827-4.
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.
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.
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.
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.
NCT02101684.
颗粒细胞卵巢肿瘤（GCTs）是一种罕见的肿瘤，其特征为FOXL2基因发生特征性突变。体外研究表明，这种改变会导致激素活性过度激活。因此，我们旨在确定CYP17抑制剂奥特雄酮在晚期疾病中的活性。
我们设计了一项多中心开放标签的II期临床试验。符合条件的患者为患有晚期或不可切除GCTs的成年女性。主要目标是临床获益率，定义为影像学有反应且疾病稳定超过6个月的患者的平均值。
2014年10月1日至2016年5月20日，GETTHI组的6个参与机构纳入了10名患者。由于入组率低，该研究提前终止。高达40%（95%CI[9.6 - 70.4%]）的病例疾病稳定超过6个月，其中2例超过12个月。1例患者在纳入试验29个月后数据库关闭时仍在继续接受治疗。根据独立影像学评估，按照RECIST标准，没有患者达到部分或完全缓解。该药物耐受性良好，仅1例出现3级不良事件，即恶心。
低入组率导致研究提前中断。然而，奥特雄酮取得了有前景的临床获益率，这支持了针对该肿瘤进一步开发新的激素疗法。
NCT02101684。
