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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HBO feasibility | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO | Device |
|
| 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 |
| 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 |
| 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. |
Inclusion Criteria
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
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%
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
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| Name | Affiliation | Role |
|---|---|---|
| Alan Hartford, MD | Dartmouth-Hitchcock Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dartmouth-Hitchcock | Lebanon | New Hampshire | 03756 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36404528 | Derived | 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. |
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Adverse events were not collected for historic controls.
HBO feasibility subjects were recruited from potential candidates for stereotactic radiosurgery (SRS) treatment at DHMC for brain metastases. Such patients are referred to radiation oncology by practitioners at DHMC and by physicians at outlying hospitals.
Historic Controls: Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The control population was selected based on matching variables.
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| ID | Title | Description |
|---|---|---|
| FG000 | HBO Feasibility | Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO |
| FG001 | Historic Controls | Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The matching variables (histology, lesion size, resection status, and calculated GPA) will be used to identify this control population. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | HBO Feasibility | Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO. Demographic information (Race, gender, ethnicity, and age) were collected for only the participants who were prospectively enrolled and provided informed consent. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Mean | Full Range | minutes | Approximately 30 minutes during SRS Treatment Visit |
|
Adverse events (AE) for the HBO Feasibility arm will be collected during the period from the initiation of the study procedures until the date of documented death, withdrawal of consent, or the end of the study, whichever occurs first. Collection could span approximately 5 years. Adverse events were not collected for the historic controls.
Symptomatic treatment toxicity: AEs potentially related to intracranial SRS and/or HBO treatments Radiographic evidence for radionecrosis/treatment effects in normal tissue identified by diagnostic radiologist of follow-up MRI imaging. Incidence of WBRT, Incidence of repeat SRS to the index site and a distant site. Local and distant disease recurrence at the treatment site identified by diagnostic radiologist of follow-up MRI imaging. AEs were not collected for historic controls.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HBO Feasibility | Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alan Hartford, MD, PhD, FACR, Professor of Medicine (RadOnc) Director, Radiation Oncology | Dartmouth-Hitchcock Medical Center | 603-650-6600 | Alan.C.Hartford@Hitchcock.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 17, 2020 | Apr 19, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| 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 |
| 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 |
| Historic Controls |
Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The matching variables (histology, lesion size, resection status, and calculated GPA) will be used to identify this control population. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Overall Survival in Years | Median time to death | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Median | Full Range | Years | 5 year from treatment |
|
|
|
| Secondary | Number of Years Until Local Recurrence | Number of years until recurrence of lesion | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Median | Full Range | Years | 5 year from treatment |
|
|
|
| Secondary | Number of Years Until Local Recurrence Prior to WBRT | Number of years until local recurrence of lesion prior to whole brain radiation therapy | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Median | Full Range | Years | 5 year from treatment |
|
|
|
| Secondary | Number of Participants Developing Intercranial Distant Recurrence | Number of participants who developed intercranial distant recurrence | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Count of Participants | Participants | 5 year from treatment |
|
|
|
|
| Secondary | Number of Months Between SRS Treatment and Whole Brain Radiation Therapy | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. 17 participants in the HBO group, and 14 historical controls did not receive whole brain radiation therapy | Posted | Median | Full Range | Months | 5 year from treatment |
|
|
|
| Secondary | Number of Lesions Exhibiting Radionecrosis | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. | Posted | Number | Lesions exhibiting radionecrosis | 5 year from treatment | Lesions | Lesions |
|
|
|
|
| Other Pre-specified | 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. | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. This information was not available for historical controls. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years |
|
|
|
| Other Pre-specified | 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. | Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. This information was not available for historical controls. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years |
|
|
|
| Other Pre-specified | Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage) | Serum markers for tissue apoptosis and for neuronal damage | Sample donations where optional for the study participants. Insufficient samples were obtained and therefore, samples were not analyzed. | Posted | 24-48 hours after the SRS treatment |
|
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| 8 |
| 19 |
| 0 |
| 19 |
| 5 |
| 19 |
| EG001 | Historic Controls | Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The matching variables (histology, lesion size, resection status, and calculated GPA) will be used to identify this control population. | 0 | 19 | 0 | 19 | 6 | 19 |
| Seizure | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Cognitive Disturbance | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Memory Impairment | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment |
|
| Intercranial hemorrhage | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Facial muscle weakness | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Concentration impairment | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| Dysarthria | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Dysphasia | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |