Treatment of Opioid-refractory Pain (WHO Level III) by Pituitary Radiosurgery

Study Overview
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Brief Summary
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80% of palliative care cancer patients suffer from severe pain. The management of these pain improves the quality of life of these patients. The management of opioid pain refractory to date remains a difficulty for caregivers. Hypophysectomy performed to try to control hormone-dependent neoplasia also help relieve pain associated with lesions secondary cancer. The surgical hypophysialis radio Gamma Knife ® was recently performed on a small number of patients. She would have the advantage of reducing the risk of complications compared to other techniques and achieve similar analgesic effect on diffuse, or mixed nociceptive pain associated with metastases on average in 2 days and would reduce or stop opiates most often responsible for side effects impairing the quality of life. The objective of this clinical trial, multicenter, prospective, randomized controlled is to evaluate the effectiveness of surgical hypophysialis radio for patients in palliative situations with refractory cancer pain in opioid level III. The type of pain cancer pain was done in order to optimize the recruitment and homogenization of the study population: patients cared for in palliative care units are mostly patients cancer (70-80%). This study is therefore part of a palliative setting and the results of this test can be extrapolated to other populations of palliative patients with refractory pain.

Official Title
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Treatment of Opioid-refractory Pain (WHO Level III) by Pituitary Radiosurgery: A Multicenter, Prospective, Randomized Study

Conditions
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Any Cancer With Multiple Bone Metastases

Intervention / Treatment
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* Device: GammaKnife®
* Device: 18F-2-fluoro-2-deoxy-D-glucose - positron emission tomography (FDG-PET)
* Device: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman, aged 18 years or older; Subject suffering from nociceptive or mixed pain, not related to acts, refractory to standard opioid therapy Subject having a cancer defined by histology whatever the origin of the primitive cancer, Subject having multiple bone metastases Subject in palliative care state according to the definition given by the French Society of Palliative Care and Support Subject supported by structures of palliative care, pain or cancer involved in the study Inpatient and outpatient Subject without a curative cancer treatment and with or without palliative anticancer treatment; Subject non in ultimate phase (estimated survival superior at 48 h by a physician) Subject with acceptable general condition (Karnofsky performance Status Scale superior at 40 Subject with a preserved vigilance defined from the Epworth scale Subject with preserved cognition according to the scale Basic Test Concentration, Memory and Guidance (TELECOM) Subject which can fill in a questionnaire, able to read or to understand the French language; Subject who signed an informed consent; Subject affiliated to the French health insurance system. Exclusion Criteria: Subject with a curative cancer treatment Subject in ultimate phase (estimated by the physician of survival less than 48 hours) History of whole brain radiation History of radiosurgery of pituitary lodge Subject treated there less than a month by external or metabolic radiotherapy analgesic, surgical analgesic technic Subject minor, pregnant or breastfeeding, subject not being affiliated to the French health insurance system or private about freedom; Subject refusing to participate in the study or not signing the informed consent. Subject allergic to any component of Fludeoxyglucose (18F) Subject allergic to gadolinium salts. Subject with severe renal impairment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pituitary radiosurgery group<br>Subjects will receive a pituitary radiosurgery by GammaKnife® during a brief hospitalization associated with standards of care for pain according to recommendations (Standards, Options and Recommendations about drug analgesic treatments for nociceptive cancer pain in adults) | Device: GammaKnife®<br> <br> Device: 18F-2-fluoro-2-deoxy-D-glucose - positron emission tomography (FDG-PET)<br> <br> Device: MRI<br> <br> |
| Active Comparator: Control group<br>Subject will receive standards of care for pain according to recommendations (Standards, Options and Recommendations about drug analgesic treatments for nociceptive cancer pain in adults) | Device: 18F-2-fluoro-2-deoxy-D-glucose - positron emission tomography (FDG-PET)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pain assessment | using the Numeric Pain Intensity Scale (NPSI) | 36 months | 
| The pain assessment | Neuropathic pain questionnaire (DN4) | 36 months | 
| The pain assessment | Self-reported pain and Quality of life | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of the visual fields | visual perimeter test | 36 months | 
| assessment of the visual acuity | exploration test macular function | 36 months | 
| endocrine balance | Rate of Corticotropic in the blood | 36 months | 
| endocrine balance | Rate of Gonadotropic in the blood | 36 months | 
| endocrine balance | Rate of Somatotropic in the blood | 36 months | 
| endocrine balance | Rate of Thyrotropic in the blood | 36 months | 
| Pituitary morphology | MRI with gadolinium | 36 months | 
| evaluate metabolic consumption of glucose | FDG-PET | 36 mois | 
| evaluate metabolic connectivity at resting-state | 18F-2-fluoro-2-deoxy-D-glucose - positron emission tomography (FDG-PET) | 36 mois |