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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Charlotte
Rawcliffe
+44 151 794 8167
raptor@liverpool.ac.uk
Prof
Richard
Shaw
+44 151 794 8938
rjshaw@liverpool.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
Osteoradionecrosis (bone death caused by irradiation)
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Most treatments for head and neck cancer include radiotherapy, and despite advances in planning and doses, this leaves survivors at risk of significant late effects. One of the most severe complications is osteoradionecrosis (ORN), which is bone death caused by irradiation. This can affect any bone or cartilage in the head and neck but is commonest in the lower jaw. ORN is characterized by exposure and crumbling of the jaw, severe pain, repeated infections, weight loss, restricted mouth opening, difficulty in chewing and disfigurement. Existing treatments include supportive and conservative methods such as long-term antibiotics, antiseptic mouthwash and painkillers, and surgery which may be curative but is risky, complex and has unpredictable outcomes. Some studies of osteoradionecrosis suggest that a combination of three medications (pentoxyphylline, tocopherol, clodronate: PENTOCLO) may be capable of complete resolution without surgery. Healing in this way is through lifting off of the dead bone fragments leaving intact skin underneath. Some research suggests that just over half of patients benefit, but this has yet to be proved, particularly in comparison with other treatments. This study proposes to compare PENTOCLO medications against standard supportive medications such as antibiotics, mouthwash and painkillers.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
You may not be able to take part if:
Current exclusion criteria as of 09/01/2024:
1. Cannot swallow tablets2. Prior treatment with PENTOCLO or any element thereof within 12 months of the date of randomisation3. Very early ORN (<20 mm² exposed bone) occurring within 12 months of a dental extraction or other dentoalveolar operation (‘Minor Bone Spicules’)4. Mandibular pathological fracture secondary to ORN5. Indication for mandible resection - i.e. patient for whom the severity of their ORN symptoms already constitute an indication for mandible resection and reconstruction. Typically, these symptoms will include severe pain, repeated infections, significant mobile pathological fracture or distressing fistula)6. Patient has had definitive resection / reconstruction for mandibular ORN -i.e. no longer has exposed necrotic bone present.7. Pregnancy8. Lactation9. Age <18 years10. Acute infection at site of the necrotic bone.11. Contraindications to PENTOCLO medications:11.1. Known hypersensitivity, allergy or anaphylaxis to pentoxifylline, tocopherol or sodium clodronate11.2. Treated hypotension11.3. Severe coronary artery disease, defined as grade IV of the Canadian Cardiology Society Angina Grading11.4. Severe atrial fibrillation, defined as grade 4 on modified CCC-SAF11.5. Myocardial infarction within 6 months11.6. Prior history of extensive retinal haemorrhage11.7. Prior history of intracranial bleeding11.8. Impaired renal function (Creatinine clearance <30 ml/minute, will be formally assessed only if U&E out of reference)11.9. Severe liver failure (class B or C Pugh-Child Score, will be formally assessed only if LFT values, out of reference)11.10. Concomitant prescription of anti-platelet agents: clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs, acetylsalicylates (ASA/LAS) including aspirin >75 mg*, ticlopidine, dipyridamole. (*low dose ≤75 mg aspirin is permitted)11.11. Concomitant prescription of ketorolac, cimetidine, ciprofloxacin, theophylline, estramustine phosphate11.12. Hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency11.13. Concomitant prescription other bisphosphonates e.g. risedronate, alendronate, aIbandronate, zoledronic acid, pamidronate, etidronate or prescription of denosusamab11.14. Concomitant prescription of aminoglycoside antibiotics e.g. gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, paromomycin
_____
Previous exclusion criteria:
1. Cannot swallow tablets 2. Prior treatment with PENTOCLO or any element thereof within 12 months of the date of randomisation3. Very early ORN (<20 mm² exposed bone) occurring within 12 months of a dental extraction or other dentoalveolar operation (‘Minor Bone Spicules’ see flowchart below)4. Mandibular pathological fracture secondary to ORN5. Extra-oral communicating fistula secondary to ORN6. Prior surgery/jaw resection7. Pregnancy8. Lactation9. Age <18 years10. Acute infection at site of the necrotic bone. 11. Contraindications to PENTOCLO medications:11.1. Known hypersensitivity, allergy or anaphylaxis to pentoxifylline, tocopherol or sodium clodronate11.2. Treated hypotension11.3. Severe coronary artery disease, defined as grade IV of the Canadian Cardiology Society Angina Grading11.4. Severe atrial fibrillation, defined as grade 4 on modified CCC-SAF11.5. Myocardial infarction within 6 months11.6. Prior history of extensive retinal haemorrhage11.7. Prior history of intracranial bleeding11.8. Impaired renal function (Creatinine clearance <30 ml/minute, will be formally assessed only if U&E out of reference)11.9. Severe liver failure (class B or C Pugh-Child Score, will be formally assessed only if LFT values, out of reference) 11.10. Concomitant prescription of anti-platelet agents: clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs, acetylsalicylates (ASA/LAS) including aspirin >75 mg*, ticlopidine, dipyridamole. (*low dose ≤75 mg aspirin is permitted)11.11. Concomitant prescription of ketorolac, cimetidine, ciprofloxacin, theophylline, estramustine phosphate11.12. Hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency11.13. Concomitant prescription other bisphosphonates e.g. risedronate, alendronate, aIbandronate, zoledronic acid, pamidronate, etidronate or prescription of denosusamab11.14. Concomitant prescription of aminoglycoside antibiotics e.g. gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, paromomycin
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Prof
Richard
Shaw
+44 151 794 8938
rjshaw@liverpool.ac.uk
Dr
Charlotte
Rawcliffe
+44 151 794 8167
raptor@liverpool.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by University of Liverpool and funded by National Institute for Health Research Efficacy and Mechanism Evaluation Programme.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 53806
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