Clinical trial NCT05795647: The PENTO Protocol in Medication-related Osteonecrosis of the Jaw
Official title: The PENTO Protocol in Medication-related Osteonecrosis of the Jaw
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Medication-related Osteonecrosis of the Jaw (MRONJ)
Keywords: MRONJ
pentoxifylline
tocophérol
bone exposure
renutrition
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2023-04-03
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Medication-related osteonecrosis of the jaw (MRONJ) occurs after taking bisphosphonates or targeted therapies. It leads to a significant decrease in quality of life with pain, eating and chewing disorders, and malnutrition. Current treatments are only partially effective. PENTO (pentoxifylline and tocopherol) has been shown to be effective in maxillary osteoradionecrosis. The objective of this study is to evaluate the proportion of bone recovery in patients receiving PENTO in MRONJ at 12 months.

Detailed description: MRONJ is defined as intraoral bone exposure persisting for more than 8 weeks after taking an anti-resorptive agent (per os or IV bisphosphonates, targeted therapies) and without history of maxilla radiotherapy or metastasis. It leads to a significant decrease in quality of life with significant pain at rest and during mastication, and compromised nutrition, sometimes resulting in severe undernutrition in patients already weakened by a history of cancer. Current treatments (prolonged antibiotic therapy, repeated bone curettage) have shown partial effectiveness. PENTO (combination of pentoxifylline, a vasodilator, and tocopherol, vitamin E) has been shown to significantly reduce intraoral exposed bone surface area and pain in maxilla osteoradionecrosis. All studies conducted so far on PENTO in MRONJ are retrospective or involve small samples. Therefore, our idea is to perform a well-conducted prospective phase IIa study to prove the efficacy of PENTO, with a larger sample size and identical follow-up periods. The investigators will study patients with AAOMS stage 2 MRONJ (exposed bone in symptomatic patients, without pathologic fracture).

Treatment will consist of pentoxifylline LP 400 mg morning and evening, combined with tocopherol 500 mg morning and evening. Antibiotic therapy with Augmentin (or clindamycin) will be added for the first month and then punctually if signs of local infection appear.

The primary and secondary endpoints will be assessed at inclusion and at 1, 3, 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

* Age greater than or equal to 18 years
* Current or past treatment with bisphosphonates (oral or IV) and/or targeted therapies (denosumab, bevacizumab)
* Signs and symptoms for more than 8S with confirmation that the signs and symptoms are not of dental origin
* AAOMS Stage 2 MRONJ
* For patients of childbearing age, effective contraception is required

Exclusion Criteria:

* History of head or neck radiotherapy or maxilla metastases
* Patients who have received treatment in the past (PENTO or PENTOCLO protocol)
* Patients who have undergone surgery for their MRONJ within the last 3 months
* Pregnant or wishing to be pregnant, breastfeeding
* Patient under palliative care
* Patient with hypersensitivity to pentoxifylline or tocopherol or to an excipient
* History of hypersensitivity reaction to penicillins, cephalosporins, or other beta-lactams (and clindamycin or lincomycin if applicable) or excipient of amoxicillin-a. clavulanic or clindamycin
* History of jaundice/hepatic injury related to amoxicillin/clavulanic acid
* Patient taking oral anticoagulants, or with a history of major bleeding or bleeding disorders
* Patient taking platelet aggregation inhibitor, theophylline or aminophylline
* Patient taking methotrexate, probenecid, mycophenolate mofetil, myorelaxant drugs, macrolide or streptogramin antibiotics
* Patients with hepatic failure or renal failure (Cl \< 30 mL/min),
* Patient with hypotension (SBP \< 90 mmHg)
* Refusal to participate in the study
* Patient participating in other interventional research that may interfere with the conduct of this research
* Patient unable to understand the protocol
* Patient under curatorship or guardianship

Primary outcomes:
measure: Exposure bone area (EBA)
timeFrame: Month 12
Secondary outcomes:
measure: SOMA score
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Nutritional parameters evolution (albuminemia)
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Nutritional parameters evolution (pre-albuminemia)
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Nutritional parameters evolution (weight)
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Nutritional parameters evolution (BMI)
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Exposure bone area (EBA)
timeFrame: Month 1, Month 3, Month 6, Month 12
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
timeFrame: Month 1, Month 3, Month 6, Month 12
Other outcomes:
Locations:
city: Limoges
country: France
facility: Limoges university hospital
Study officials:
affiliation: University Hospital, Limoges
name: Julie USSEGLIO, Dr
role: PRINCIPAL_INVESTIGATOR
References: