Clinical trial NCT06746103: RELIEVE: Research on Effectiveness of Surgery and Radiotherapy on Relieving Spine Tumor Pain in Patients with Vertebral Metastases
Official title: RELIEVE Research on Effectiveness of Surgery and Radiotherapy on Relieving Spine Tumor Pain in Patients with Vertebral Metastases
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Spinal Metastasis
Lead sponsor: AO Foundation, AO Spine
Sponsor class: OTHER
First posted: 2024-12-24
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with metastatic spinal tumors as per eligibility criteria.

Brief summary: This is a prospective, multicenter, observational study focusing on assessing and managing pain in patients with metastatic spinal tumors. Pain from spinal metastases adversely impacts quality of life, function, and treatment outcomes. Advances in surgical techniques have shown significant benefits. However, previous studies either lacked nuanced differentiations or simply categorized pain as mechanical or non-mechanical; explaining the highly variable pain outcome measurements in these studies. This study employs the AO Spine Cancer-Related Pain Classification to better categorize neoplastic spinal pain by etiology.

Detailed description: This is a prospective, multicenter, observational study. Patients with metastatic spinal tumors and one symptomatic metastatic site (ie, the index metastasis) that is causing at least one type of pain (ie, the index pain) of interest to this study that has at least "moderate" pain in intensity (numeric rating scale \[NRS\] \> 4) will be enrolled from participating sites. Four types of neoplastic pain in the AO Spine Cancer-Related Pain Classification are of interest to this study.

1. The axial non-triggered pain is hypothesized to be secondary to periosteal stretching and/or release of nociceptive cytokines; it is mostly associated with osteoclastic activity but can be sometimes associated with reactive sclerosis. This pain may show a diurnal variation with increased severity at night and typically responds to steroids or opioid medications.
2. The axial triggered/mechanical pain is nociceptive pain secondary to inability of osseous spinal structures to support physical loads. It is typically associated with osteoclastic activity but can also be due to periosteal nerve stimulation from frank fractures or microfractures. This pain typically does not respond well to the medical treatments and if the pain is severe, progressive, or debilitating, may benefit from stabilization.
3. Radicular non-triggered pain is a result of persistent compression of a nerve root which can be due to tumor or bone expansion. This type of neurologic pain follows a specific nerve root distribution with a correlative compression lesion. It may be resolved with decompression or potentially with nonoperative measures such as radiotherapy or systemic treatments.
4. Radicular triggered/mechanical pain is a result of transient compression of a nerve root caused by mechanical instability. This type of neurologic pain also follows a specific nerve root distribution with a correlative compression lesion. It may be relieved in certain position such as recumbency and often benefits from stabilization surgery with or without decompression.

Patients will be treated (ie, the index treatment) with surgery alone, surgery with postoperative radiotherapy, or radiotherapy alone for the index metastasis. Day 0 is defined as: 1) for patients receiving surgery only, the day of the surgery (or the first stage of surgery in the case of staged surgery), 2) for patients receiving radiotherapy only, the day of the first session of radiotherapy, or 3) for patients receiving both surgery and radiotherapy, whichever treatment day that comes earlier. Patients will be followed up at 1 month, 3 months, and 6 months after Day 0. The primary study outcome is the intensity of the four different types of pain caused by the index spinal metastasis. The study will delineate how these kinds of pain respond to treatment over time. Secondary objectives investigate factors predictive of pain relief and the relationship between pain and other patient-reported outcomes (PROs).

Eligibility criteria: Inclusion Criteria:

* Age 18 years and older
* Patients diagnosed with metastatic spinal tumors with one index metastatic site that, confirmed by the treating clinicians, is causing spine pain
* Patients experience at least one type of pain that is of interest of this study, namely, axial non-triggered pain, axial triggered/mechanical pain, radicular non-triggered pain, and radicular triggered/mechanical pain
* At least one type of the pain experienced has an NRS \> 4 of 10
* Patients undergoing surgery and/or radiotherapy

  * Surgery may be instrumented stabilization surgery alone, instrumented stabilization and decompression, or decompression surgery alone.
  * Percutaneous screw fixation counts as instrumented stabilization surgery.
  * Any kind of radiotherapy is includable.
* Ability to provide informed consent according to the IRB/EC defined and approved procedures

Exclusion Criteria:

* Estimated survival \< 3 months
* Patients with more than one symptomatic spine metastasis site

  o An example is a patient with two metastasis sites: a lumbar metastasis (causing vertebral fracture and epidural compression leading to mechanical lower back pain and static radicular pain to legs) and a cervical metastasis (causing tumor-related pain at the neck).
* Patients with other sources of pain that may confound the measurement of the primary outcome

  o An example is a patient with liver metastasis which causes visceral pain that can confound the thoracic spinal pain caused by the spinal metastasis.
* Patients undergoing the following treatments alone without the surgeries listed in the inclusion criteria or radiotherapy

  * Cement augmentation, vertebroplasty, kyphoplasty, and other emerging interventions such as local ablative technique
  * Chemotherapy or systemic therapy alone

Primary outcomes:
measure: Pain intensity on the Brief Pain Inventory Intensity Scale of four different types of pain caused by the index spinal metastasis, measuring pain on a numeric rating scale from 0 to 10, with 0 meaning no pain and 10 meaning as bad as one can imagine.
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Patient Reported Outcome Measure: Michigan Body Map measuring pain location
timeFrame: Baseline, 1 month, 3 months, and 6 months
measure: Patient Reported Outcome Measure: PainDETECT measuring neuropathic pain
timeFrame: Baseline, 1 month, 3 months, and 6 months.
measure: Patient Reported Outcome Measure: BAT measuring breakthrough pain
timeFrame: Baseline, 1 month, 3 months, and 6 months.
measure: Patient Reported Outcome Measure: PROMIS Bank v1.0-Fatigue measuring fatigue
timeFrame: Baseline, 1 month, 3 months, and 6 months.
measure: Patient Reported Outcome Measure: PROMIS Bank v2.0-Physical Function measuring physical function
timeFrame: Baseline, 1 month, 3 months, and 6 months.
measure: Patient Reported Outcome Measure: RAPA measuring physical activity
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: SOSGOQ v2 measuring health-related quality of life
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: GAD-7 measuring anxiety
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: PHQ-8 measuring depression
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: PROMIS Bank v1.0-Sleep Disturbance measuring sleep
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: PCS -6 measuring pain catastrophizing
timeFrame: Baseline and 3 months.
measure: Patient Reported Outcome Measure: PEPSO measuring patient expectations
timeFrame: Baseline.
measure: Patient Reported Outcome Measure: PGIC scale measuring global improvement with treatment
timeFrame: 1 month, 3 months, and 6 months.
measure: Time up and go test measuring mobility
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: 30-second sit-to-stand test measuring mobility
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: 6-minute walk test measuring mobility
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Walking speed measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Speed variability measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Cadence measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Step length measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Stride length measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Step length symmetry measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Single support measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Stance measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Stance asymmetry measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Double support measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Double support asymmetry measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Step width measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Stride consistency measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Hip range of motion measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Femoral rotation range measuring gait
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Survival
timeFrame: Baseline, 1 month, 3 months and 6 months
measure: Tumor control
timeFrame: Baseline, 1 month, 3 months and 6 months
Other outcomes:
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