Oncology Department, Gustave-Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif, France.
Hôpitaux Universitaires Paris Nord Val de Seine (HUPVNS), Paris, France.
Target Oncol. 2017 Oct;12(5):655-661. doi: 10.1007/s11523-017-0525-2.
Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors.
This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment.
Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%).
This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer.
NCT01743469.
他喹莫德是一种具有免疫调节、抗血管生成和抗转移特性的小分子药物，针对肿瘤微环境。本研究旨在获得临床概念验证，证明他喹莫德在晚期实体瘤患者中具有活性和可耐受性。
这项早期停止设计、开放性、概念验证临床试验评估了他喹莫德在四组晚期肝癌（n=53）、卵巢癌（n=55）、肾癌（n=38）和胃癌（n=21）患者中的临床活性。他喹莫德每天口服（至少 2 周 0.5mg/天，剂量增加至 1mg/天），直至根据实体瘤反应评估标准 1.1 （RECIST）标准出现影像学进展、无法耐受毒性或患者退出。主要疗效终点是根据 RECIST 1.1 进行中央评估的无进展生存期（PFS）率。
在 8 周（胃癌队列为 6 周）进行的中期无效性分析发现，他喹莫德仅在肝癌队列中具有足够的临床活性，因此停止了对其他三个队列的招募。PFS 率分别为肝癌、卵巢癌、肾癌和胃癌队列的 16 周时 26.9%、24 周时 7.3%、16 周时 13.2%和 12 周时 9.5%。在试验的第二阶段，肝癌队列的预设 PFS 阈值未达到。最常见的治疗相关不良事件是疲劳（48.5%）、恶心（34.1%）、食欲下降（31.7%）和呕吐（24.6%）。
本研究未能证明他喹莫德在晚期肝癌、卵巢癌、肾癌和胃癌的大量预处理患者中具有临床活性。
NCT01743469。
