Hyperbaric oxygen plus PENTOCLO for jaw bone damage after radiation

Combination Therapy: Hyperbaric Oxygen and PENTOCLO for Treatment of Osteoradionecrosis of the Mandible, a Pilot Randomized Control Trial

This trial will test if adding a year-long PENTOCLO medicine regimen to hyperbaric oxygen helps people with osteoradionecrosis of the mandible heal better than hyperbaric oxygen alone.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (other)
• Drugs / interventions: denosusamab, Radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06055257 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, open-label, outcome-blinded pilot trial that will enroll adults with confirmed mandibular osteoradionecrosis and randomize them 1:1 to receive standard hyperbaric oxygen therapy (HBOT) alone or HBOT plus a modified PENTOCLO oral regimen. Participants must be able to undergo up to 60 HBOT sessions at a specialized clinic and will receive the oral regimen for at least one year when assigned. The primary objective is to determine feasibility for a larger definitive trial by measuring recruitment, adherence, 12-month follow-up completion, ability to collect outcome measures, and study costs, while also recording clinical outcomes such as pain and adverse events. Randomization is stratified by ORN stage and the trial is conducted at a single center.

Who should consider this trial

Good fit: Adults (≥18) with confirmed mandibular osteoradionecrosis (exposed devitalized irradiated bone >20 mm2), who have not received prior ORN treatments, have an in-date ECG, negative baseline pregnancy test if applicable, and are able and willing to complete up to 60 HBOT sessions.

Not a fit: People who have already had treatment for ORN (PENTOCLO, HBOT, or surgery), who plan major surgery, or who cannot safely undergo HBOT are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination could improve jaw healing, reduce pain and complications, and lower the need for more invasive surgery in patients with mandibular ORN.

How similar studies have performed: HBOT and PENTOCLO have each been used as adjuvant treatments for ORN with some supportive reports, but combining them is novel and has not been tested in randomized trials before.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of mandibular ORN after completion of radiotherapy
* ORN will be defined as "an area of exposed devitalized irradiated bone (\> 20 mm2)"; minor bone spicules (MBS) (\< 20 mm2) in the absence of radiographic abnormality, will be considered clinically insignificant
* Has no contraindications for undergoing hyperbaric oxygen therapy as assessed by a Hyperbaric Physician, and is willing to commit the time to undergo 60 sessions
* Negative Human Chronic Gonadotropin (hCG) screening test at baseline (for female patients of reproductive age not practicing medically acceptable methods of birth control (e.g., hormonal contraceptives, implants, injectables, intrauterine device (IUD), intrauterine system (IUS), vasectomy and bilateral tubal ligation)
* Baseline in-date ECG (within 60 days prior to enrolment)
* Age ≥ 18

Exclusion Criteria:

* Inability to give informed consent
* Previous treatment for ORN (PENTOCLO, HBOT or surgery)
* Major surgical procedure planned (more extensive than sequestrectomy)
* Severe trismus and inability to obtain intraoral photographs
* Contraindications for HBOT: pneumothorax, bullous disease, uncontrolled hypertension, uncontrolled epilepsy, claustrophobia
* Contraindications to mPENTOCLO (inability to swallow medication; pregnancy or lactating; allergy to any study drug; currently on oral anticoagulants; hemorrhagic/coagulation disorder; Vitamin K deficiency; active unresolved cardiac disease; severe liver or kidney disease (CrCl\<30 mL/min))
* Known QT prolongation as documented on an in-date ECG (within 60 days prior to enrolment) are excluded. Patients with the QTc prolongation associated with a correctable cause (e.g., electrolyte imbalance or drug-induced), and corrected QTc prior to enrolment into the study as documented on 12 lead ECG will be eligible for inclusion
* Patients requiring concurrent use of medications known to significantly prolong the QT interval with a high risk of clinical impact (e.g., erythromycin, cisapride, astemizole, pimozide or quinidine) are excluded unless safe discontinuation or substitution of these medications is feasible prior to initiation of the study
* Patients on medication with a potential but low risk of QTc prolongation (e.g., ondansetron, SSRIs) may be included if a post-initiation ECG conducted within 24-48 hours of starting ciprofloxacin or fluconazole confirms that there is no significant QTc prolongation
* History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanate
* Moderate to severe active liver disease (class B or C Pugh-Child Score) or active liver disease with significant acute elevation of LFT values
* History of myasthenia gravis
* Patients with a history of nontraumatic tendon disorders with severe functional impairment (i.e., significant swelling of the affected tendon, or partial tendon tear documented on clinical examination or imaging)
* Patients who have previously experienced peripheral neuropathy due to exposure to antibiotics
* Smokers, high alcohol intake (average of \>2 standard drinks per day), sepsis, severe undernourishment and severe immunodeficiency conditions (e.g. HIV, autoimmune disease, immune-compromised)
* Persistent or recurrent cancer and active neoplastic pathology will be excluded
* Patients with documented Vitamin K deficiency
* Patients taking additional Vitamin E
* Patients with concomitant prescription of anti-resorptive or anti-angiogenic medications (e.g. risedronate, alendronate, aIbandronate, zoledronic acid, pamidronate, etidronate or prescription of denosusamab, etc.)
* Patients diagnosed with retinitis pigmentosa
* Patients diagnosed with clinically significant anemia

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Ben Safa, MD — Sunnybrook Health Sciences Centre
• Study coordinator: Ben Safa, MD

Conditions: Osteoradionecrosis, Osteoradionecrosis of Jaw, Osteoradionecrosis of the Mandible, ORN, PENtoxifylline, TOcopherol and CLOdronate, PENTOCLO, Hyperbaric Oxygen Therapy, HBOT