Clinical trial NCT01850563: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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 .
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2013-05-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The Average Time From HBO Chamber Exit to SRS beam-on
timeFrame: Approximately 30 minutes during SRS Treatment Visit
Secondary outcomes:
measure: Overall Survival in Years
timeFrame: 5 year from treatment
measure: Number of Years Until Local Recurrence
timeFrame: 5 year from treatment
measure: Number of Years Until Local Recurrence Prior to WBRT
timeFrame: 5 year from treatment
measure: Number of Participants Developing Intercranial Distant Recurrence
timeFrame: 5 year from treatment
measure: Number of Months Between SRS Treatment and Whole Brain Radiation Therapy
timeFrame: 5 year from treatment
measure: Number of Lesions Exhibiting Radionecrosis
timeFrame: 5 year from treatment
Other outcomes:
measure: Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS)
timeFrame: Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
measure: Average Score of EORTC Global Health Status (QL2)
timeFrame: Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
measure: Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage)
timeFrame: 24-48 hours after the SRS treatment
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Alan Hartford, MD
role: PRINCIPAL_INVESTIGATOR
References: