Hyperbaric Oxygen + PENTOCLO for Osteoradionecrosis

Overseen By Ben Safa, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Oral anticoagulants, QT prolongers

Disqualifiers: Previous ORN treatment, Severe liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for osteoradionecrosis (ORN), a serious side effect of radiation therapy for head and neck cancer. The trial compares standard hyperbaric oxygen therapy (HBOT) with a new approach that adds a modified PENTOCLO treatment, which includes several antibiotics and other medications taken for a year. The goal is to determine if adding PENTOCLO to HBOT reduces pain, side effects, and the need for surgery more effectively than HBOT alone. This trial is best suited for individuals with ORN in the jaw after cancer radiation who can commit to attending 60 HBOT sessions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking certain medications, especially those that significantly prolong the QT interval or involve oral anticoagulants. If you are on medications with a low risk of QT prolongation, you may still participate if an ECG shows no significant issues after starting the study drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PENTOCLO is effective and safe for treating osteoradionecrosis (ORN), a condition affecting the jawbone after radiation therapy. Past studies demonstrated healing in 54% to 100% of patients. The treatment eased symptoms and reduced the need for surgery. Importantly, long-term use of PENTOCLO is considered safe. It aids in healing both the moist tissue lining the mouth and the bone, providing significant symptom relief.

Although data on using hyperbaric oxygen therapy (HBOT) with modified PENTOCLO together is not yet available, each has shown promise individually. HBOT is often used and is safe, though it requires many sessions. Combining these treatments aims to improve outcomes for people with ORN. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the modified PENTOCLO treatment for osteoradionecrosis (ORN) because it offers a new approach that combines an oral regimen with standard hyperbaric oxygen therapy (HBOT). Unlike traditional treatments that primarily focus on HBOT and conservative measures like local irrigation and antiseptic mouthwash, mPENTOCLO introduces a comprehensive oral regimen aimed at enhancing recovery. This treatment stands out due to its unique combination of pentoxifylline, tocopherol, and clodronate, which work together to improve blood flow, reduce inflammation, and support bone healing. By addressing the condition from multiple angles, mPENTOCLO has the potential to be more effective than the standard of care alone.

What evidence suggests that the combination of hyperbaric oxygen and modified PENTOCLO could be effective for osteoradionecrosis?

Research has shown that the PENTOCLO treatment can effectively heal osteoradionecrosis (ORN). In studies, up to 100% of patients fully healed, with many experiencing fewer symptoms and needing less surgery. One study found that 54 patients with ORN completely recovered after about nine months of PENTOCLO treatment. In this trial, participants in the intervention group will receive the modified PENTOCLO (mPENTOCLO) treatment, which includes a mix of antibiotics and other medications taken over a year, alongside standard care. Overall, PENTOCLO has shown promise in helping patients heal and feel better. ^{2 3 4 6 7}

Who Is on the Research Team?

Ben Safa, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with mandibular osteoradionecrosis after radiotherapy, who can undergo hyperbaric oxygen therapy (60 sessions) and have a recent ECG. Women of childbearing age must have a negative pregnancy test and use birth control.

Inclusion Criteria

I am 18 years old or older.

I have bone damage in my jaw after finishing radiation therapy.

I can undergo hyperbaric oxygen therapy and can commit to 60 sessions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants undergo a 4-week pre-treatment phase with oral antibiotics as part of the mPENTOCLO regimen

4 weeks

Treatment

Participants receive standard care with 60 hyperbaric oxygen therapy (HBOT) treatments and a comprehensive mPENTOCLO regimen

12 months

5 visits per week for HBOT, additional visits as needed for mPENTOCLO

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-ups at 4 weeks, 5/6 weeks, and 3, 6, 9, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• modified PENTOCLO

Trial Overview The study tests if combining hyperbaric oxygen therapy (HBOT) with modified PENTOCLO—a mix of antibiotics and oral meds—is more effective than HBOT alone in treating bone death caused by radiation in the jaw.

How Is the Trial Designed?

Group I: Group 2 (Intervention) Experimental Treatment 1 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.

Group II: Group 1 (Control) Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40208822/

Efficacy of PENTOCLO Therapy in Treating Head & Neck ... The selected main outcomes to determine the efficacy of PENTOCLO therapy were wound healing status after treatment, reduction in the percentage ...

2. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-025-08966-9

RAPTOR: Randomised Controlled Trial of PENTOCLO ... [9] showed 54 patients with ORN experienced complete resolution of early ORN after a median of 9 months treatment with the PENTOCLO protocol.

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/01455613251381176

A Comprehensive Review of the PENTOCLO Protocol and ... In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06055257

NCT06055257 | Combination Therapy: Hyperbaric Oxygen ... This will be the first study to investigate the potential benefits of combining HBOT and a modified PENTOCLO regimen for treatment of ORN. This study is a ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301610005146

Complete Restoration of Refractory Mandibular ... Long-term PENTOCLO treatment is effective, safe, and curative for refractory ORN and induces mucosal and bone healing with significant symptom improvement.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12291413/

RAPTOR: Randomised Controlled Trial of PENTOCLO ... The secondary outcomes measures include the determination of the impact of PENTOCLO on the deterioration of ORN, analgesia and antibiotic usage, ...

7. raptorstudy.org.uk raptorstudy.org.uk/files/RAPTOR%20Protocol%20V4.0%2019022024.pdf

RAPTOR: Randomised Controlled Trial of PENTOCLO* in ... This phase II proposal will establish the first robust signal of efficacy, an estimate of effect size, and the safety/tolerability of PENTOCLO ...