The Baromedical Research Foundation

Study Components

The study is comprised of two separate investigations:

Phase I Trial

Initially, we will undertake a dose escalation investigation. The purpose of this is to determine the optimal degree to which patients can undergo pre-radiation hyperbaric oxygen. We are hopeful that they will tolerate the full five days per week protocol employed by radiotherapy. There is evidence that this is achievable in brain cancer studies. We will determine if this is the case in head and neck cancers.

Three patients will undergo hyperbaric oxygen therapy on a Monday and Friday only schedule. If they are able to tolerate this without any increase in commonly anticipated toxicity, then the next three patients will receive pre-radiation hyperbaric oxygen on Monday, Wednesday and Friday. If tolerance remains acceptable, the final three patients will receive hyperbaric oxygen Monday through Friday. We are hopeful that this latter regimen will be the case.

Hyperbaric dosing:

Radiotherapy:

Chemotherapy:

Phase III Trial

Upon conclusion of the Phase I trial, a Phase III trial will be instituted. It is anticipated that five daily hyperbaric oxygen exposures will be achieved. The Phase III protocol is based upon this assumption, and will be revised if this is not the case. The Phase III trial will be a randomized, double-blind prospective trial.

Study Groups:

  1. Conventional standard care (radiotherapy and chemotherapy) immediately preceded by hyperbaric oxygen;
  2. Conventional standard care immediately preceded by sham hyperbaric oxygen

Required Sample Size:

54 patients in study group A (Conventional standard care i.e. radiotherapy and chemotherapy immediately preceded by hyperbaric oxygen)

54 patients in study group B (Conventional standard care immediately preceded by sham hyperbaric oxygen)

Objectives:

Primary Outcomes* -

 Protocol compliance
Progression-free survival at 2 years:

Overall survival at 2 years

Secondary Outcomes* -

Quality of Life
Adverse effects of hyperbaric oxygen
Incidence of acute radiation toxicity
Incidence of late radiation tissue injury at 2 years

*Evaluating physician blinded to treatment / placebo allocation

Hyperbaric Oxygen:

Group A - 2.4 ATA oxygen for 30 minutes
Compression rate (breathing oxygen): per patient tolerance; 1 – 3 psi per minute
Decompression rate (breathing oxygen) at 2-3 psig/fsw per minute

Group B - Brief compression to 5 psig breathing air at 1 psi per minute, then
slow decompression to 1 psig breathing air at 1 psi per minute and hold for 45 minutes*

Three lead ECG monitoring throughout

Interval between exiting chamber and ‘beam on’ not to exceed 15 minutes

* difference in time to accommodate for longer compression / decompression times in Group A and to further facilitate patient blinding

Radiation Therapy:

 IMRT of 70 Gray in 35 fractions, at 2 Gray per fraction

Chemotherapy:

Cisplatin (30 mg / m 2 IV once per week)

Pathology:

Specimens will include tumor tissue samples, blood and urine samples obtained at different intervals during the study. Blood and urine will be analyzed for multiple biologic markers to correlate with the response to HBO therapy trial arm. Tumor tissue samples will be analyzed to determine whether there is a predictive susceptibility of tumors to HBO sensitization using currently defined biomarkers known to correlate with survival.

Tissue -
Collect tumor specimen prior to initiation of treatment

Tissue biomarkers –
EGFR, Cyclin D1, Bcl-2, p53, for correlation with overall survival.
Performed by immunohistochemistry on 80 samples (one per patient)