卵巢癌在妇科癌症中死亡率最高，主要是因为它通常在晚期才被诊断出来，并且由于复发性疾病会产生化疗耐药性。改善铂类耐药卵巢癌女性的预后是一项尚未得到满足的重大需求。皮质醇激活糖皮质激素受体 (GR) 已被证明可以抑制细胞毒性药物使用的细胞凋亡途径，从而限制其功效。选择性 GR 调节可能能够抵消皮质醇的抗细胞凋亡作用，从而增强化疗的疗效。之前的一项 2 期研究表明，在白蛋白结合型紫杉醇中添加间歇给药的 Relacorilant（一种选择性 GR 调节剂）可改善复发铂类女性患者的结局，包括无进展生存期 (PFS) 和总生存期 (OS)，且附加毒性最小耐药卵巢癌。 ROSELLA 研究旨在在更大的人群中证实并扩展这些发现。ROSELLA 是一项 3 期、随机、2 组、开放标签、全球多中心研究，对象是患有复发性、铂类耐药、高级别浆液性上皮性卵巢癌的女性、原发性腹膜癌或输卵管癌。符合资格的参与者之前已接受过 1 至 3 种全身抗癌治疗，包括≥1 种先前的铂类治疗和先前的贝伐珠单抗治疗，且有记录显示疾病进展或对最近的治疗不耐受。对于参与者的选择没有基于生物标志物的要求。参与者以 1:1 的比例随机接受间歇性给药的 relacorilant 联合白蛋白结合型紫杉醇或白蛋白结合型紫杉醇单一疗法。该研究的主要疗效终点是通过盲法独立中央审查评估的 PFS。次要疗效终点包括 OS、研究者评估的 PFS、客观缓解率、最佳总体缓解、缓解持续时间、24 周时的临床受益率和癌症抗原 125 缓解。该研究还在评估安全性和患者报告的结果。ClinicalTrials.gov 标识符：NCT05257408；欧盟药物监管机构临床试验数据库标识符：2022-000662-18。© 2024。亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。

Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinum-resistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol's antiapoptotic effects, enhancing chemotherapy's efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population.ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nab-paclitaxel or nab-paclitaxel monotherapy. The study's primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18.© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.