通过体外药物筛选实现胶质母细胞瘤个性化靶向治疗：高级脑肿瘤治疗临床试验（ATTRACT）研究方案
Personalized targeted glioblastoma therapies by ex vivo drug screening: Study protocol of the Advanced brain Tumor TheRApy Clinical Trial (ATTRACT).
作者信息
Berghoff Anna Sophie, Mair Maximilian J, Spiró Zoltán, Abdel Malak Calvin, El-Heliebi Amin, Eckert Franziska, Furtner Julia, König Franz, Leibetseder Annette, Nowosielski Martha, Oberndorfer Stefan, Prietl Barbara, Pichler Josef, Pieber Thomas R, Spiegl-Kreinecker Sabine, Urbanic Purkart Tadeja, Wöhrer Adelheid, Widhalm Georg, Preusser Matthias
机构信息
Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Precision Medicine Technologies, CBmed GmbH, Graz, Austria.
出版信息
Neurooncol Adv. 2025 Mar 7;7(1):vdaf056. doi: 10.1093/noajnl/vdaf056. eCollection 2025 Jan-Dec.
BACKGROUND
Novel approaches to guide personalized treatment in glioblastoma are urgently needed. Given the poor predictive value of genetic biomarkers in glioblastoma, we are conducting a prospective clinical trial to investigate the novel approach of cultivated patient-derived tumor cells (PDCs) for ex vivo drug screening.
METHODS
In this randomized phase 2 study, we are testing the ability of PDC-based ex vivo drug screening to formulate a personalized recommendation for maintenance treatment in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter after combined radio-chemotherapy. Based on overall survival as the primary endpoint, we plan to include 240 patients (120 per group) to show with a power of 80% that we can increase the median survival from 12 to 17 months (hazard ratio 0.7). Patients will be randomized 1:1 to either the standard group (no drug screening) or the intervention group (drug screening and personalized recommendation for maintenance treatment). In the intervention group, automated drug screening will be performed on PDCs with 28 drugs used for the treatment of solid tumors and hematological malignancies. Based on the cytotoxic activity of these drugs, as quantified by relative viability based on adenosine triphosphate levels, a molecular tumor board will recommend a personalized treatment regimen.
RESULTS
The first patient was enrolled in July 2024. Interim analysis of the ATTRACT study (NCT06512311) is expected in late 2027, and final results in 2030.
TRIAL REGISTRATION
The ATTRACT trial is registered under the ID NCT06512311 (https://clinicaltrials.gov/study/NCT06512311).
背景
胶质母细胞瘤急需新的方法来指导个性化治疗。鉴于基因生物标志物在胶质母细胞瘤中的预测价值不佳，我们正在开展一项前瞻性临床试验，以研究培养患者来源的肿瘤细胞（PDC）用于体外药物筛选的新方法。
方法
在这项随机2期研究中，我们正在测试基于PDC的体外药物筛选为新诊断的、MGMT启动子未甲基化的胶质母细胞瘤患者在放化疗后维持治疗制定个性化推荐的能力。以总生存期作为主要终点，我们计划纳入240例患者（每组120例），以80%的检验效能表明我们能够将中位生存期从12个月提高到17个月（风险比0.7）。患者将按1:1随机分为标准组（无药物筛选）或干预组（药物筛选及维持治疗的个性化推荐）。在干预组中，将对PDC进行自动化药物筛选，使用28种用于治疗实体瘤和血液系统恶性肿瘤的药物。根据基于三磷酸腺苷水平的相对活力定量的这些药物的细胞毒性活性，分子肿瘤专家委员会将推荐个性化治疗方案。
结果
首例患者于2024年7月入组。预计2027年末对ATTRACT研究（NCT06512311）进行中期分析，最终结果于2030年得出。
试验注册
ATTRACT试验已在ID为NCT06512311（https://clinicaltrials.gov/study/NCT06512311）的网站注册。
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