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

Primary Purpose

Brain Metastases

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases focused on measuring Demonstrate coordination of HBO with SRS treatments is feasible., Demonstrate outcomes for patients treated with combination of HBO and SRS are non-inferior .

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dartmouth-Hitchcock

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

HBO feasibility

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
May 7, 2013
Last Updated
January 19, 2022
Sponsor
Dartmouth-Hitchcock Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01850563
Brief Title
A Proof-of-principle Study of HBO-SRS for Brain Metastases
Official Title
A Proof-of-principle Study of Hyperbaric Oxygen as a Radiosensitizer Prior to Stereotactic Radiosurgery for Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
July 1, 2013 (Actual)
Primary Completion Date
October 3, 2019 (Actual)
Study Completion Date
February 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dartmouth-Hitchcock Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases
Keywords
Demonstrate coordination of HBO with SRS treatments is feasible., Demonstrate outcomes for patients treated with combination of HBO and SRS are non-inferior .

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HBO feasibility
Arm Type
Other
Intervention Type
Device
Intervention Name(s)
Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO
Primary Outcome Measure Information:
Title
The Average Time From HBO Chamber Exit to SRS beam-on
Description
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
Time Frame
Approximately 30 minutes during SRS Treatment Visit
Secondary Outcome Measure Information:
Title
Overall Survival in Years
Description
Median time to death
Time Frame
5 year from treatment
Title
Number of Years Until Local Recurrence
Description
Number of years until recurrence of lesion
Time Frame
5 year from treatment
Title
Number of Years Until Local Recurrence Prior to WBRT
Description
Number of years until local recurrence of lesion prior to whole brain radiation therapy
Time Frame
5 year from treatment
Title
Number of Participants Developing Intercranial Distant Recurrence
Description
Number of participants who developed intercranial distant recurrence
Time Frame
5 year from treatment
Title
Number of Months Between SRS Treatment and Whole Brain Radiation Therapy
Time Frame
5 year from treatment
Title
Number of Lesions Exhibiting Radionecrosis
Time Frame
5 year from treatment
Other Pre-specified Outcome Measures:
Title
Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS)
Description
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.
Time Frame
Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Title
Average Score of EORTC Global Health Status (QL2)
Description
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.
Time Frame
Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Title
Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage)
Description
Serum markers for tissue apoptosis and for neuronal damage
Time Frame
24-48 hours after the SRS treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Hartford, MD
Organizational Affiliation
Dartmouth-Hitchcock Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth-Hitchcock
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States

12. IPD Sharing Statement

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

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