Shaw Richard, Knight Ruth, Basoglu Ayten, Bajwa Mandeep, Perry Julie, Kanatas Anastasios, Fedele Stefano, Killen Vincent, Tangney Rebecca, Butterworth Chris, McCaul James, Dhanda Jagtar, Patel Vinod, Evans Mererid, Jackson Richard
Liverpool Head & Neck Centre, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
Trials. 2025 Jul 24;26(1):254. doi: 10.1186/s13063-025-08966-9.
Mandibular osteoradionecrosis (ORN) is a severe late radiation toxicity affecting 5-10% of patients who receive radiotherapy as part of treatment for head and neck malignancy. ORN can cause permanent disfigurement, dysfunction, pain and infection. There remains little robust evidence supporting the efficacy of medical or surgical management currently offered in clinical practice. Retrospective case series and meta-analyses of observational studies suggest that a repurposed triple drug combination pentoxifylline-tocopherol-clodronate ('PENTOCLO') may be effective in preventing deterioration, promoting healing and ultimately reducing the need for major reconstructive surgery.
The RAPTOR trial is a phase II, open-label, multicentre, randomised controlled trial with a superiority design. Eligible subjects with mandibular ORN are randomised 1:1 to receive standard of care (Arm A) or PENTOCLO plus standard of care (Arm B) for 12 months. The primary outcome measure is time from randomisation to healing of ORN (without the need for surgery), as measured by clinical examination (confirming completely healed oral mucosa), intra-oral clinical photographs and imaging. RAPTOR has an embedded translational sample collection and a methodological component exploring the use of electronic patient-reported outcome measures (ePROM).
The RAPTOR trial is the first randomised controlled clinical trial of PENTOCLO in this clinical setting. The results of this phase II trial will provide robust preliminary evidence on its efficacy and inform the feasibility and appropriateness of a subsequent definitive trial.
RAPTOR is registered with the ISRCTN registry effective date 11th November 2022: Clinical trial of the non-surgical management of radiotherapy damage to the lower jaw ISRCTN34217298, and also registered with the European Clinical Trials Database (Eudra-CT 2022-000728-39).
下颌骨放射性骨坏死（ORN）是一种严重的晚期放射毒性反应，影响着5%至10%接受放疗作为头颈恶性肿瘤治疗一部分的患者。ORN可导致永久性毁容、功能障碍、疼痛和感染。目前临床实践中提供的药物或手术治疗的疗效，几乎没有有力证据支持。回顾性病例系列研究和观察性研究的荟萃分析表明，一种重新利用的三联药物组合己酮可可碱 - 生育酚 - 氯膦酸盐（“PENTOCLO”）可能有效预防病情恶化、促进愈合，并最终减少大型重建手术的需求。
RAPTOR试验是一项II期、开放标签、多中心、具有优效性设计的随机对照试验。符合条件的下颌骨ORN患者按1:1随机分组，接受12个月的标准治疗（A组）或PENTOCLO加标准治疗（B组）。主要结局指标是从随机分组到ORN愈合（无需手术）的时间，通过临床检查（确认口腔黏膜完全愈合）、口腔内临床照片和影像学检查来衡量。RAPTOR试验有一个嵌入式转化样本收集和一个探索使用电子患者报告结局指标（ePROM）的方法学部分。
RAPTOR试验是PENTOCLO在这种临床环境下的首个随机对照临床试验。该II期试验的结果将为其疗效提供有力的初步证据，并为后续确定性试验的可行性和适宜性提供参考。
RAPTOR已在ISRCTN注册中心注册，生效日期为2022年11月11日：下颌骨放疗损伤的非手术治疗临床试验，ISRCTN34217298，同时也在欧洲临床试验数据库（Eudra - CT 2022 - 000728 - 39）注册。
