A Proof-of-principle Study of HBO-SRS for Brain Metastases

NCT ID: NCT01850563

Last Updated: 2022-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-01
• Study Completion Date: 2020-02-28

Brief Summary

Patients with brain metastases who are candidates for treatment with stereotactic radiosurgery (SRS) are potential study participants. SRS delivers high-energy, precisely-focused radiation to each brain metastasis to shrink the tumor, and is the standard-of-care for patients with these tumors. Oxygen enhances the damaging effects of radiation on tumor cells. Hyperbaric oxygen (HBO) therapy increases oxygen levels in all kinds of tissues, including tumors. The purpose of this trial is to study whether it is feasible to treat patients with HBO just prior to receiving SRS, given the timing constraints of treating sequentially with HBO and then SRS. Patients will undergo HBO treatment followed by the placement of a Gill-Thomas-Cosman head frame then transported ,via stretcher, to receive SRS. The transfer and placement of the head frame needs to be completed within the 15minute time frame. The trial's secondary objectives are to determine whether it has any effects on outcomes and quality of life. As part of study participation patients will be asked to complete quality of life questionnaires as well as mini mental status questionnaires. These will be done prior to treatment and at follow up appointments throughout the next 3 years while participating in the study. Patients will be given the option to participate in the optional bio marker blood draw study which would require patients to have blood drawn at three time points, pre-treatment, the day after treatment and at their first follow up visit.

Conditions

Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HBO feasibility

Group Type: OTHER

Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO

Intervention Type: DEVICE

Interventions

Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Metastatic brain tumor referred to radiation oncology for treatment
• Size of the presenting metastatic lesion up to 5.0 cm diameter
• Age > 18 years
• Patients must give informed consent indicating they are aware of the investigational nature of this treatment
• Karnofsky Performance Status > 70% (Zubrod score 0 to 1)
• Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days to start of study therapy
• CBC and CMP within 30 days to start of study therapy
• Chest imaging (Chest Xray or Chest CT) within past 12 months, that does not show any contraindication to hyperbaric therapy (if patient has had any thoracic surgery or other significant event that might have affected the thorax such as trauma, pneumothorax, chest tube insertion, pleurodesis, or thoracentesis and has not had imaging since that event, then the imaging should be repeated).
• Neurosurgery Consult

Exclusion Criteria

• Pregnant women or women of childbearing potential without adequate contraception. Contraception, which can include abstinence, is required since the last menstrual period until completion of SRS.
• Evidence of pneumothorax (Untreated pneumothorax risks tension pneumothorax during ascent in HBO chamber)
• COPD with C02 retention (Such patients can develop respiratory depression as HBO reduces their hypoxemic drive)
• Uncontrolled seizure disorder (Note that patients on adequate antiepileptic medications may receive HBO)
• Claustrophobia resistant to medication (Pre-medication with anxiolytics is generally sufficient for almost all anxious patients undergoing HBO treatment)
• History of middle ear surgery

• Failure to equalize pressure in the middle ear can cause displacement of middle ear structures with consequent hearing loss
• To clarify: placement of a tympanostomy tube is not a contraindication to HBO, and in fact may improve tolerability of the procedure
• History of bleomycin administration (HBO can exacerbate interstitial pneumonitis in such patients)
• Current cis-platinum chemotherapy, i.e. therapeutic levels in the bloodstream at the time of HBO therapy. (HBO can increase cytotoxicity of cis-platinum)
• Uncontrolled high blood pressure (HBO can increase systemic vascular resistance)
• Unstable angina or myocardial infarction within the previous 3 months (Increased afterload due to HBO can increase myocardial workload)
• Cardiac EF ≤ 35%

• Pulmonary edema can arise with HBO in certain patients with severe heart failure
• In patients with prior history of CHF, subsequent echocardiogram and ECG are required to establish EF>35%
• Treatment with disulfiram (Disulfiram inhibits superoxide dismutase and is not approved for use concomitantly with hyperbaric oxygen therapy)
• Active drug/alcohol dependence or abuse
• Lack of adequate social support structures, e.g. homelessness
• Tumors with potential confounding results on serum marker studies

• Small cell (neuroendocrine) carcinomas
• Carcinoid tumors

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Alan Hartford

Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alan Hartford, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock

Lebanon, New Hampshire, United States

Countries

United States

References

Hartford AC, Gill GS, Ravi D, Tosteson TD, Li Z, Russo G, Eskey CJ, Jarvis LA, Simmons NE, Evans LT, Williams BB, Gladstone DJ, Roberts DW, Buckey JC Jr. Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study. Radiother Oncol. 2022 Dec;177:179-184. doi: 10.1016/j.radonc.2022.10.024. Epub 2022 Oct 28.

Reference Type: DERIVED

PMID: 36404528 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

D12129

Identifier Type: -

Identifier Source: org_study_id