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

A Proof-of-principle Study of Hyperbaric Oxygen as a Radiosensitizer Prior to Stereotactic Radiosurgery for Brain Metastases

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.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Device: Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HBO feasibility	Device: Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Average Time From HBO Chamber Exit to SRS beam-on	Time from end of HBO decompression to start of SRS treatment will be measured to determine feasibility. Feasibility is defined as having been achieved if more than 50% of the 20 evaluable patients start SRS treatment within 30 minutes of leaving the HBO tank	Approximately 30 minutes during SRS Treatment Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival in Years	Median time to death	5 year from treatment
Number of Years Until Local Recurrence	Number of years until recurrence of lesion	5 year from treatment
Number of Years Until Local Recurrence Prior to WBRT	Number of years until local recurrence of lesion prior to whole brain radiation therapy	5 year from treatment
Number of Participants Developing Intercranial Distant Recurrence	Number of participants who developed intercranial distant recurrence	5 year from treatment
Number of Months Between SRS Treatment and Whole Brain Radiation Therapy		5 year from treatment
Number of Lesions Exhibiting Radionecrosis		5 year from treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS)	SLUMS is an 11-item screening tool to evaluate cognitive ability in adults. The SLUMS score ranges from 1-30. For patients with a high school education, the normal range score is 27-30. For mild neurocognitive disorder, the score range is 21-26. Dementia range is 1-20. For patients with less than a high school education the normal range score is 25-30. For mild neurocognitive disorder, the score range is 20-24. Dementia range is 1-19. The scores across all time points were averaged to obtain the mean.	Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Average Score of EORTC Global Health Status (QL2)	Averages score QL2 determined by responses to aggregate combined results of questionnaires (QLQ C-30 and BN-20). EORTC Quality of Life Questionnaire C-30 (QLQ C-30): 30-item self-report questionnaire rating items on a 4-point scale (1 "not at all" to 4 "very much") It measures several domains (physical, role, emotional, cognitive, and social functioning, fatigue, pain, nausea and vomiting) and several single items. Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better QoL on global health status and functional scales and worse QoL on symptom scales and financial difficulty scale. EORTC QLQ BN-20 (BN-20): 4 scales comprised of multiple items and 7 single items. All items are rated on a 4-point Likert-type scale, 1=not at all' to 4=very much, and linearly transformed to a 0-100 scale, higher scores indicating more severe symptoms. The scores across all time points were averaged to obtain the mean.	Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage)	Serum markers for tissue apoptosis and for neuronal damage	24-48 hours after the SRS treatment

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: Alan Hartford, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): October 3, 2019
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: May 7, 2013
• First Submitted That Met QC Criteria: May 8, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Demonstrate coordination of HBO with SRS treatments is feasible.; Demonstrate outcomes for patients treated with combination of HBO and SRS are non-inferior .
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: D12129

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes