Recruiting
Phase 3

HBOT & PENTOCLO

Sponsor:

Sunnybrook Health Sciences Centre

Code:

NCT06055257

Conditions

Osteoradionecrosis

Osteoradionecrosis of Jaw

Osteoradionecrosis of the Mandible

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

modified PENTOCLO (mPENTOCLO)

sham mPENTOCLO

Study Details

Brief 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.

Conditions

Osteoradionecrosis

Osteoradionecrosis of Jaw

Osteoradionecrosis of the Mandible

Study ID

NCT06055257

Start date

Jan 16, 2025

Status verified date

Sep, 2025

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

24 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Group 1 (Control)

Standard of care treatment for ORN consisting of conservative measures (e.g. local irrigation, antiseptic mouthwash) and approximately 60 hyperbaric oxygen therapy (HBOT) treatments (90 minute exposures at 2.4 ATA each, scheduled Monday to Friday for 12 weeks - i.e., 5 treatments per week). At the conclusion of the study and at the discretion of the clinical team, patients randomized to the control group with residual disease may be considered for the mPENTOCLO protocol.

Simultaneously, the 4-week mPENTOCLO "pre-treatment" phase will be started (as defined in the intervention section), followed by a sham/placebo mPENTOCLO treatment phase for a total of 12 months.

experimental: Group 2 (Intervention)

Standard of care treatment as described for the control group (conservative measures and 60 HBOT treatments).

Simultaneously, a comprehensive oral regimen (mPENTOCLO) will be started, including a 4-week "pre-treatment phase" followed by a "treatment phase" for a total of 12 months, as defined in the Intervention section.

Interventions

modified PENTOCLO (mPENTOCLO)

4-week "pre-treatment" phase consisting of 2 g daily of Amoxicillin+Clavulanic acid 875/125 mg (1 g morning and night), 1 g ciprofloxacin (500 mg morning and night) and 50 mg Fluconazole daily (morning), taken orally by the patient.

This is followed by an additional 11 months (12 months total) "treatment" phase consisting of 800 mg pentoxifylline (400 mg morning and night) and 800 IU tocopherol (400 IU morning and night) taken orally 5 days per week (Monday to Friday with no medications on Saturday and Sunday). If the patient deteriorates (i.e., worsening of ORN T 6 or 9-month follow-up) then clodronate 1600 mg once daily (Monday to Friday) for the rest of the study period will be added.

sham mPENTOCLO

4-week "pre-treatment" phase consisting of 2 g daily of Amoxicillin+Clavulanic acid 875/125 mg (1 g morning and night), 1 g ciprofloxacin (500 mg morning and night) and 50 mg Fluconazole daily (morning), taken orally by the patient.

This is followed by an additional 11 months (12 months total) of sham "treatment" phase (placebo).

Primary outcome measure

  • Recruitment and adherence to protocol (process) [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Recruitment and adherence to protocol (process) [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Recruitment and adherence to protocol (process) [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Recruitment and adherence to protocol (process) [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Recruitment and adherence to protocol (process) [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Feasibility (resource) - Time [ Time Frame: Pilot study (including 12-month follow-up) ]
  • Feasibility (resource) - Cost [ Time Frame: Pilot study (including 12-month follow-up) ]

Central Contacts and Locations

Central contacts

Ben Safa, MD

416-480-4864ben.safa@sunnybrook.ca

Locations

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N3M5

Contacts

Ben Safa

416 480 4864ben.safa@sunnybrook.ca

More Information

Sponsor

Sunnybrook Health Sciences Centre

Last update posted

Sep 12, 2025

Last verified

Sep, 2025

Keywords

  • Osteoradionecrosis
  • ORN
  • PENtoxifylline, TOcopherol and CLOdronate
  • PENTOCLO
  • Hyperbaric Oxygen Therapy
  • HBOT
  • Head and Neck Cancer
  • Radiation Therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sunnybrook Health Sciences Centre on 2025-09-12.