OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020.

中文翻译：

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OptimalTTF-2 研究方案：通过颅骨重塑手术增强肿瘤治疗野以治疗首次复发的胶质母细胞瘤：一项 2 期、多中心、随机、前瞻性、介入试验


OptimalTTF-2 是一项随机、比较、多中心、研究者发起的介入研究，旨在测试颅骨重塑手术与肿瘤治疗场疗法 (TTFields) 相结合，以及最佳医生选择的肿瘤内科疗法治疗胶质母细胞瘤患者的首次复发。 OptimalTTF-2 是一项于 2020 年 11 月启动的 2 期试验。颅骨重塑手术由五个钻孔组成，每个钻孔直径为 15 毫米，位于肿瘤切除腔的正上方。临床前研究表明，该程序可显着增强肿瘤治疗场的效果。我们最近完成了一项 1 期安全/可行性试验，表明总体生存率有所提高，并且没有额外的毒性。该二期试验旨在验证所提议干预措施的有效性。该试验被设计为比较性、1:1 随机、最小最大两阶段第 2 阶段，预计有 70 名患者，最大样本量为 84 名患者。对前 52 名患者进行 12 个月的随访后，将进行中期无效性分析。两个试验组将包括 a) TTFields 疗法结合最佳医生选择的肿瘤治疗（对照组）或 b) 颅骨重塑手术、TTFields 疗法和最佳肿瘤学实践（介入组）。主要资格标准包括年龄≥18岁、幕上胶质母细胞瘤第一次复发、卡诺夫斯基评分≥70、局灶性肿瘤以及缺乏明显的合并症。研究设计旨在检测 12 个月后总生存率 (OS12) 提高 20%，假设对照组 OS12 = 40%，干预组 OS12 = 60%。 次要终点包括总生存率和无进展生存率的风险率、客观肿瘤缓解率、生活质量、KPS、类固醇剂量和毒性。每三个月评估一次毒性、客观肿瘤缓解率和生活质量。终点数据将在试验结束时收集，包括疑似意外严重不良反应（SUSAR）、不可接受的严重不良事件（SAE）、撤回同意或失访的发生情况。首次复发的胶质母细胞瘤非常需要新的治疗方式。我们提出的颅骨重塑手术、肿瘤治疗场和最佳实践肿瘤医学治疗的治疗方式可能会显着提高总体生存率。 ClinicalTrials.gov 标识符：NCT0422399，注册日期：2020 年 1 月 13 日。