Clinical trial NCT02368457: Management of Mandibular ORN: PENTO as Medical Treatment
Official title: Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoradionecrosis
Keywords: Mandibular osteoradionecrosis
Tocopherol
pentoxifylline
vitamine E
wounds and injuries
antioxidants
free radical scavengers
radiation-protective agents
vasodilatadors agents
osteonecrosis
mandible
extraoral fistula
exposed bone
necrotic bone
head and neck radiotherapy
Lead sponsor: Hospital Vall d'Hebron
Sponsor class: OTHER
First posted: 2015-02-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mandibular osteoradionecrosis, despite its low incidence, remains being the most problematic and irreversible complication after head and neck radiotherapy with no medical treatment to limit or reduce symptoms.

Different clinical trials have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis. This study proposes to use this drugs to determine if there is healing of mandibular osteoradionecrosis and/or a symptomatic improvement as well.

Detailed description: Mandibular osteoradionecrosis which occurs after the use of radiation therapy for the treatment of head and neck cancer remains being the most problematic and irreversible complication despite its low incidence with no medical treatment to limit or reduce symptoms.

Clinical trials conducted to date have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis that have been irradiated based on the properties of this drugs in increased tissue oxygenation and their antioxidant effect.

The aim of this study is to determine if there is a clinical improvement of mandibular osteoradionecrosis using Pentoxifylline in combination with Tocopherol as treatment because, currently, there is no effective treatment to achieve bone healing and/or a symptomatic improvement.

Eligibility criteria: Inclusion Criteria:

* Over 18 years and under 90 years old.
* Patients who have received radiotherapy after being diagnosed with head and neck cancer and currently are diagnosticated of mandibular osteoradionecrosis (any clinical stage)
* Follow-up for at least a year after the radiation treatment is completed.
* Absence of tumor at the time of recruitment.
* Patients with the capacity to give informed consent

Exclusion Criteria:

* Allergy or hypersensitivity to Pentoxifylline or others xanthines, or to Tocopherol (vitamin E).
* Patients taking oral anticoagulants (acenocoumarol, warfarin).
* Known hemorrhagic/coagulation disorder.
* Vitamin K deficiency due to any cause.
* Use of estrogens oral contraceptives.
* Serious bleeding or extensive retinal hemorrhage.
* Ischaemic heart diseases, including recent Myocardial Infarction.
* Serious cardiac arrhythmia.
* Severe LIVER DISEASE.
* Severe renal failure (creatinine clearance \<30 mL/min).
* Hypotension.
* Female patients who are pregnant or lactating
* Any other situation or condition that, in the opinion of the INVESTIGATOR, may interfere with optimal PARTICIPATION in the study.

Primary outcomes:
measure: Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG).
timeFrame: From baseline to 1, 3, 6, and 9 months of starting treatment
Secondary outcomes:
measure: Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale
timeFrame: From baseline to 1,3, 6, 9 months of starting treatment
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebrón Hospital
Study officials:
affiliation: Oral and Maxillofacial Surgery (Vall d'Hebrón Hospital)
name: Miriam Martos-Fernandez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robard L, Louis MY, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Dec;131(6):333-338. doi: 10.1016/j.anorl.2013.11.006. Epub 2014 Jun 30.
citation: Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):832-9. doi: 10.1016/j.ijrobp.2010.03.029. Epub 2010 Jul 16.
citation: Delanian S, Depondt J, Lefaix JL. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck. 2005 Feb;27(2):114-23. doi: 10.1002/hed.20121.