Clinical trial NCT03894553: Focused Ultrasound (FUS) Mesencephalotomy for Head & Neck Cancer Pain
Official title: Stereotactic MRI-guided Focused Ultrasound Mesencephalotomy for Pain Palliation in Head & Neck Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cancer of Head and Neck
Pain, Face
Pain, Neck
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2019-03-28
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This proposed pilot study will investigate the safety and initial effectiveness of focused ultrasound lesioning of the contralateral mesencephalon for severe, opioid-resistant pain associated with head and neck cancer

Detailed description: This pilot study is designed as a prospective, open-label clinical trial of stereotactic FUS mesencephalotomy in 6 subjects with treatment-refractory pain from head and neck cancer. Primary safety assessments will be made throughout the study period of 6 months following the procedure. Primary efficacy outcome is determined by comparing the difference in baseline NPRS to 3 months post treatment. All subjects receiving treatment will be followed for the six month study period.

Eligibility criteria: Inclusion Criteria:

1. Men and women, between 18 and 75 years, inclusive
2. Subjects with head and neck cancer, including one of the following:

   * Cancer that arises in the head and neck region: nasal cavity, sinuses, lips, mouth, salivary glands, throat, or larynx (typically squamous cell carcinoma)
   * Cancer occurring in the nasopharynx, skin, thyroid gland, and eye
   * Lymphoma
   * Sarcoma
3. Craniofacial or cervical pain related to the cancer that meets all of the following criteria:

   * Severe defined by: Worst NPRS score of ≥ 5 out of 10 at current visit and the subject reports having a similar level of pain for at least the past two months.
   * Pain is medication-refractory to all three tiers of the WHO cancer pain ladder. Thus, adequate trials of at least 3 prescription medications that will include a 'weak' and a 'strong' opioid. An adequate medication trial is defined as a therapeutic dose of each medication without sufficient effect.
   * Duration of greater than 6 months
4. Mesencephalon contralateral to the pain can be targeted by the ExAblate Neuro device. The region of the mesencephalon must be apparent on MRI. Additional MRI sequences including inversion-recovery and DTI may be utilized to refine the target.
5. Subjects who are able and willing to give consent and able to attend all study visits
6. Subjects who are able to communicate sensations during the focused ultrasound treatment

Exclusion Criteria:

1. Idiopathic trigeminal neuralgia
2. Trigeminal neuropathic pain from trauma, infection, or iatrogenic
3. Post-herpetic neuralgia
4. Headache syndromes like migraine, cluster headache
5. Temporomandibular joint syndrome
6. Atypical facial pain or pain related to a somatoform disorder
7. Subjects deemed poor candidates by a multidisciplinary team of cancer and palliative care clinicians:

   1. Significant clinician concern about reliability of subject-reported information, such as subject in active process of seeking disability for neuropathic pain
   2. Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-V as manifested by one (or more) of the following occurring within a 12 month period: Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household). Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)
   3. Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
   4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
8. Subjects with active psychiatric illness will be excluded. For the purpose of this study, active psychiatric illness includes:

   1. Exhibiting current suicide ideation and/or a history of suicide attempt within past 2 years
   2. been hospitalized for the treatment of a psychiatric illness within the past 2 years
   3. received transcranial magnetic stimulation for depression treatment
   4. received electroconvulsive therapy for depression
   5. any presence or history of psychosis
9. Subjects with unstable cardiac status including:

   1. Unstable angina pectoris on medication
   2. Subjects with documented myocardial infarction within six months of protocol entry
   3. Significant congestive heart failure defined with ejection fraction \< 40
   4. Subjects with unstable ventricular arrhythmias
   5. Subjects with atrial arrhythmias that are not rate-controlled
10. Severe hypertension (diastolic BP \> 100 on medication)
11. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
12. On medications that increases the bleeding risk, based on the published guidelines which are currently recognized by the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine and the North American Neuromodulation Society (Reg Anesth Pain Med 2015;40: 182-212); specifically:

    1. Aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abciximab) for the last 7 days prior to treatment.
    2. Oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours.
    3. Intravenous or subcutaneous heparin-derived compounds for the last 48 hours.
13. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hours of total table time.)
14. Subjects participating or have participated in another clinical trial in the last 30 days
15. Subjects with risk factors for intraoperative or postoperative bleeding from a documented coagulopathy or if their serum coagulation studies (platelet count, PT, PTT, and INR) exceed the institutional laboratory limits.
16. Subjects with brain tumors or any significant intracranial mass.
17. Any illness that in the investigator's opinion preclude participation in this study
18. Pregnancy or lactation
19. Legal incapacity or limited legal capacity
20. Subjects with a deep brain stimulation implant
21. Skull density ratio, calculated from the baseline non-contrasted head CT, is less than 0.4
22. History of hemorrhagic stroke or cerebrovascular event within the past year of treatment exhibiting incomplete resolution
23. Subjects whose primary pain is other than craniofacial neuropathic pain.
24. Patients deemed high risk because of their airway for the procedure as evaluated by anesthesia.

Primary outcomes:
measure: Adverse Events
timeFrame: 6 months post-intervention
measure: Numeric Pain Rating Scale
timeFrame: 3 months post-intervention (will also be assessed at 7 days, 1 month, and 6 months post-intervention)
Secondary outcomes:
measure: Patient Global Impression of Change
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS scale v1.0 - Pain Intensity 3a
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS scale v2.0 - Neuropathic Pain Quality 5a
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS scale v2.0 - Nociceptive Pain Quality 5a
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS scale v1.0 - Pain Behavior 7a
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS scale v1.0 - Pain Interference 8a
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS - Ca Item Bank v1.0 - Emotional Distress-Anxiety
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS - Ca Item Bank v1.0 - Emotional Distress-Depression
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS - Ca Item Bank v1.0 - Fatigue
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: PROMIS - Ca Bank v1.1 - Physical Function
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: Pain Catastrophizing Scale
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: Daily morphine equivalents (milligrams)
timeFrame: Baseline, 7 days, 1 month, 3 months, and 6 months post-intervention
measure: Location of lesion in the x, y, z dimensions in mm
timeFrame: 7 days and 3 months post-intervention
measure: Precision of lesion in the x, y, z dimensions and two dimensional radial vector in mm
timeFrame: 7 days and 3 months post-intervention
measure: Volume of lesion in mm3
timeFrame: 7 days and 3 months post-intervention
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia UVA Health, University Hospital
state: Virginia
Study officials:
affiliation: University of Virginia
name: Jeff Elias
role: PRINCIPAL_INVESTIGATOR
References: