Management of Mandibular ORN: PENTO as Medical Treatment

Osteoradionecrosis Clinical Trial

— PENTO  

Official title:

Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02368457
• Other study ID #: ORN-2014-16
• Status: Completed
• Phase: Phase 4
• First received: February 10, 2015
• Last updated: February 24, 2018
• Start date: February 2016
• Est. completion date: January 1, 2018

Study information

• Verified date: February 2018
• Source: Hospital Vall d'Hebron
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 1, 2018
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoradionecrosis

Intervention

Drug:
• Pentoxifylline and Tocopherol
pentoxifylline with tocopherol Pentoxifylline 800 mg/day, oral (1cp 400 mg twice a day) + Vitamin E (alfa-tocopherol) 1000 UI/day, oral (1cp 400UI twice a day + 1cp200UI once a day) during 24 months (maximum).

Locations

Country	Name	City	State
Spain	Vall d'Hebrón Hospital	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Vall d'Hebron

Country where clinical trial is conducted

Spain, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG).	Clinical healing assessment as measured with the classification of ORN stages, area of bone exposed (mm2) and radiological findings (OPG).; Intraoral bone exposure is measured in mm2.	From baseline to 1, 3, 6, and 9 months of starting treatment
Secondary	Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale	Evaluation of symptoms improvement using the LENT-SOMA scale (Late Effect Normal Tissue Task Force / Subjective, Objective, Management, Analytic scale).; To examine the LENT/SOMA scale prospectively using interviews and questionnaires; Assessments were made from baseline to 1, 3, 6 and 9 months of starting treatments. The acceptability and feasibility of using the scales was examined using compliance in completion of the questionnaires.; Maximum score: 36 Minimum score: 0; Questionnaires have been completed for 24 patients after treatment. Higher values represents worse outcome.; Scale categories: Subjective: pain, nutritional problems, difficulty in mouth openning. Objective: bone exposure, trismus, Management: analgesic treatment, oral treatment, nutrition. Analytic: radiological findings.	From baseline to 1,3, 6, 9 months of starting treatment