Combination Therapy: Hyperbaric Oxygen and PENTOCLO for Treatment of Osteoradionecrosis of the Mandible

• Status: Not yet recruiting
• Trial end date: 2025-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Radiation is commonly used to treat cancer in the head and neck, however, this can lead to a serious complication called osteoradionecrosis (ORN), where there is necrotic (dead) open bone inside or outside of the mouth. This complication is difficult to treat, involves large healthcare costs, and can have devastating effects on quality of life.

Two common adjuncts used in treatment of ORN are hyperbaric oxygen therapy (HBOT), which may requires up to 60 treatments at a specialized clinic where patients are treated with high concentrations of oxygen using special chambers, and a less complex option called PENTOCLO which involves treating patients with several antibiotics followed by a combination of other oral medications taken for at least 1 year.

This pilot study will be guide the design of a definitive trial to examine if the combination of HBOT and a modified PENTOCLO protocol together is better than the current standard treatment of HBOT alone. Outcomes will include pain, side effects and the need for surgery in patients with ORN. Specifically, the results of this small, pilot study will help to inform the design of a future larger study.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sunnybrook Health Sciences Centre
• Treatments: Clodronic Acid; Pentoxifylline; Tocopherols

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)

• Currently on other drugs known to prolong the QT interval (e.g., erythromycin, cisapride, astemizole, pimozide or quinidine)

• History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanate

• Moderate to severe liver disease (due potential for drug induced liver dysfunction)

• History of myasthenia gravis

• Patients with a history of nontraumatic tendon disorders or have experienced nontraumatic tendinitis or tendon rupture

• 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 who have received previous anti-resorptive or anti-angiogenic medications

• Patients diagnosed with retinitis pigmentosa

• Patients diagnosed with clinically significant anemia