Shaw, R., Knight, R., Basoglu, A. et al. (12 more authors) (2025) RAPTOR: Randomised Controlled Trial of PENTOCLO (pentoxifylline-tocopherol-clodronate) in Mandibular Osteoradionecrosis—study protocol for an open-label phase II randomised controlled superiority trial. Trials, 26 (1). 254. ISSN: 1745-6215
Abstract
Background
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.
Methods
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).
Discussion
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.
Trial registration
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).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Mandible, Osteoradionecrosis, Radiotherapy, Head and neck, Cancer, PENTOCLO, Pentoxifylline, Tocopherol, Sodium clodronate, Clinical trial |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > School of Dentistry Visitors (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Aug 2025 10:37 |
Last Modified: | 07 Aug 2025 15:16 |
Published Version: | https://trialsjournal.biomedcentral.com/articles/1... |
Status: | Published |
Publisher: | Springer Nature |
Identification Number: | 10.1186/s13063-025-08966-9 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:230170 |