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Management of Mandibular ORN: PENTO as Medical Treatment (PENTO)

Primary Purpose

Osteoradionecrosis

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Pentoxifylline and Tocopherol
Sponsored by
Hospital Vall d'Hebron
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoradionecrosis focused on measuring 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

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Vall d'Hebrón Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Pentoxifylline and Tocopherol

CONTROL

Arm Description

Drug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months.

No drug treatment

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
February 10, 2015
Last Updated
February 24, 2018
Sponsor
Hospital Vall d'Hebron
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1. Study Identification

Unique Protocol Identification Number
NCT02368457
Brief Title
Management of Mandibular ORN: PENTO as Medical Treatment
Acronym
PENTO
Official Title
Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
January 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Vall d'Hebron

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pentoxifylline and Tocopherol
Arm Type
Experimental
Arm Description
Drug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months.
Arm Title
CONTROL
Arm Type
No Intervention
Arm Description
No drug treatment
Intervention Type
Drug
Intervention Name(s)
Pentoxifylline and Tocopherol
Other Intervention Name(s)
PENTO
Intervention Description
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).
Primary Outcome Measure Information:
Title
Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG).
Description
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.
Time Frame
From baseline to 1, 3, 6, and 9 months of starting treatment
Secondary Outcome Measure Information:
Title
Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale
Description
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.
Time Frame
From baseline to 1,3, 6, 9 months of starting treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miriam Martos-Fernandez, MD
Organizational Affiliation
Oral and Maxillofacial Surgery (Vall d'Hebrón Hospital)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vall d'Hebrón Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24993781
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.
Results Reference
background
PubMed Identifier
20638190
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.
Results Reference
background
PubMed Identifier
15641107
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.
Results Reference
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Management of Mandibular ORN: PENTO as Medical Treatment

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