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

ConditionsOsteoradionecrosis Osteoradionecrosis of Jaw Osteoradionecrosis of the Mandible

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

AgeNot listed

SponsorSunnybrook Health Sciences Centre

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

modified PENTOCLO (mPENTOCLO)
Drug
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
Drug
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).

Treatment groups

24 Participants

are divided into 2 treatment groups

Group A: Group 1 (Control)Placebo comparator 1 intervention

Group B: Group 2 (Intervention)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

Recruitment and adherence to protocol (process)

Recruitment of two subjects per month on average over 12 months

Time frame

Pilot study (including 12-month follow-up)

Recruitment and adherence to protocol (process)

At least 70% of all eligible patients are recruited

Time frame

Pilot study (including 12-month follow-up)

Recruitment and adherence to protocol (process)

More than 80% of all recruited subjects complete 60 sessions of HBOT (20/24)

Time frame

Pilot study (including 12-month follow-up)

Recruitment and adherence to protocol (process)

More than 80% of patients in mPENTOCLO group complete mPENTOCLO protocol (10/12)

Time frame

Pilot study (including 12-month follow-up)

Secondary outcomes

Recovery from ORN at one-year follow-up

Proportion of patients reaching recovery within the study period in each group. "Recovery" will be defined as the absence of pain, pathologic fracture, and cutaneous fistula; exposed bone area (EBA) less than 20 mm2; and by evidence of stabilization or regression on radiographic findings (Notani classification score). Minor bone spicules of less than 20 mm2 that have no ongoing pain, and no radiographic abnormalities will be considered fully healed and not Notani grade 1.

Time frame

12-month follow-up

Time required to achieve recovery in patients

Difference in time required to reach recovery in each group. "Recovery" will be defined as the absence of pain, pathologic fracture, and cutaneous fistula; exposed bone area (EBA) less than 20 mm2; and by evidence of stabilization or regression on radiographic findings (Notani classification score). Minor bone spicules of less than 20 mm2 that have no ongoing pain, and no radiographic abnormalities will be considered fully healed and not Notani grade 1.

Time frame