Department of Radiation Oncology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
Department of Neurosurgery, University Hospital of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
Radiat Oncol. 2024 Jan 22;19(1):11. doi: 10.1186/s13014-024-02408-7.
Despite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation.
We initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Münster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols.
This is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma.
This study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Münster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689).
尽管过去几十年手术和辅助治疗有所改善，但胶质母细胞瘤患者的预后仍然很差。5-氨基酮戊酸（5-ALA）诱导的卟啉已被用于荧光引导切除和光动力治疗的光敏剂。新发现揭示了它们作为增敏剂与电离辐射联合使用的潜力。
我们启动了一项 I/II 期剂量递增研究，用口服 5-ALA 联合放疗（RT）治疗复发性胶质母细胞瘤患者。这项在明斯特大学医院进行的前瞻性单中心研究旨在招募 30 名年龄在 18 岁以上、表现状态良好（KPS≥60）的幕上胶质母细胞瘤复发的患者。按照 3+3 剂量递增设计，接受再次切除的患者将接受 36 Gy RT，包括放射动力治疗（RDT）。RDT 包括在照射前口服 5-ALA。两个队列还将在手术前三天和两天各接受两次新辅助治疗。为了确定重复 5-ALA 给药的最大耐受剂量，将增加 RDT 剂量，从一个剂量增加到最大 8 个剂量，同时密切监测安全性和毒性。治疗后两个月和五个月进行随访。主要终点是重复 ALA 给药的最大耐受剂量（MTD），次要终点是无事件生存、无进展生存和总生存。此外，在整个治疗过程中分析 5-ALA 代谢物和放射生物学标志物，并在新辅助治疗后确定切除组织的组织效应。本方案符合临床试验方案的 SPIRIT 指南。
这是首例重复使用 5-ALA 作为复发性胶质母细胞瘤治疗增敏剂的人体试验，即 ALA-RDT 在 GBM 中的研究。
该研究于 2022 年 10 月 12 日获得西伐利亚利珀医师协会和明斯特大学当地伦理委员会、2022 年 10 月 13 日获得德国联邦药物和医疗器械研究所以及 2022 年 8 月 29 日获得联邦放射防护办公室的批准。该试验在欧洲公开 EudraCT 数据库（EudraCT-No：2021-004631-92）上注册，并在 www.cliniclatrials.gov 上注册（标识符：NCT05590689）。
