Clinical trial NCT04218617: Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases
Official title: Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Spine Metastases
Spine Stereotactic Radiosurgery (sSRS)
Keywords: C79.40
C79.49
C79.51
C79.52
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Spine radiosurgery (SRS) utilizes advanced treatment planning with focused x-rays to deliver one to four high dose treatments to the spine to help relieve pain and/or neurologic symptoms. Spine SRS uses special equipment to position the participant and guide the focused beams toward the area to be treated and away from normal tissue.

One of the side effects of spine SRS is the development of vertebral compression fractures, many of which are not painful. The goal of this study is to compare the effects, good and/or bad, of spine SRS given in 1 or 2 treatments. Our main goal is to find out which approach will reduce the chances of developing vertebral compression fractures.

Detailed description: The primary objective of this study is to establish the non-inferiority in vertebral compression fracture (VCF) incidence at 6 months between single-fraction and two-fraction sSRS.

Other objectives are to to evaluate the 12-month impact of single- and two-fraction sSRS on local control (LC), pain control (PC), quality of life (QOL), and toxicity (specifically, pain flare, radiation esophagitis/laryngitis/pharyngitis, and radiation myelitis)

This study is planned as a two-arm randomized phase II trial to establish non-inferiority of single fraction sSRS compared to two-fraction sSRS. Approximately 130 participants will be enrolled in this trial; 65 participants in each arm:

* Group 1: If you are assigned to this group, you will undergo spine radiosurgery in a single (1) session.
* Group 2: If you are assigned to this group, you will undergo spine radiosurgery in two (2) sessions.

Eligibility criteria: Inclusion Criteria:

* Karnofsky Performance Status (KPS) ≥ 70
* RPA class 1 (KPS \>70 AND controlled systemic disease) or RPA Class 2 (KPS \>70, uncontrolled systemic disease OR KPS ≤70, age ≥54, no visceral metastases)44 (see Appendix II)
* Vertebral metastases from C3 to L5 based on bone scan, CT, PET, or MRI.
* Vertebral metastases must be (1) solitary, (2) at two contiguous levels, or (3) a maximum of three separate sites, with a maximum of two contiguous levels.
* Radioresistant metastases are permitted (including sarcomas, melanomas, and renal cell carcinomas).
* Patients with epidural disease are permitted so long as there is no cord compression.
* Paraspinal extension is permitted, so long as the paraspinal component is ≤5 cm
* Multiple small metastatic lesions (\<20% vertebral body involvement) of no clinical correlate are permitted, and not included in the irradiated segments as per RTOG 0631
* History and physical within four weeks of registration.
* Negative pregnancy test within four weeks of registration for women of childbearing potential.
* Diagnostic spine MRI with and without contrast within four weeks of registration
* Neurological exam within four weeks of registration to rule out rapid neurological decline. Mild to moderate neurological deficits are acceptable, as long as distance between lesion and spinal cord is ≥3 mm
* Patients may have prior EBRT at the index site.
* Informed consent of the participant.

Exclusion Criteria:

* Lesions at C1-2 or S1-Coccyx.
* Hematologic malignancies including lymphoma and myeloma.
* Multiple primary cancers.
* Primary neoplasms of the spine
* Prior corpectomy, kyphoplasty/vertebroplasty, or instrumentation at the site of planned sSRS.
* Spinal cord compression.
* Paraspinal mass \>5 cm.
* Patients with rapid neurologic decline.
* Bony retropulsion resulting in neurologic deficit.
* Patients with contraindications to MRI.
* Patients allergic to intravenous contrast for MRI or CT.
* Patients with emergent spinal cord compression.
* Patients with mechanical instability of the spine.
* Patients with active connective tissue disease.
* Patients who previously underwent sSRS to the vertebrae of interest.
* Patients with diffuse or multilevel metastatic spinal disease with \>20% involvement of vertebral bodies, defined as involvement of \>5 vertebral levels.
* Inability to participate in study activities due to physical or mental limitations.
* Inability or unwillingness to return for all required follow-up visits and imaging.
* Inability to deliver sSRS, either 18 Gy in one fraction, or 24 Gy in two fractions.

Primary outcomes:
measure: 6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS
timeFrame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
Secondary outcomes:
measure: Local control (LC) as defined as absence of local progression of disease In the event of disease progression, all cases will be reviewed at the multi-disciplinary spine tumor board for a consensus recommendation
timeFrame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
measure: Pain control (PC) as assessed by the Brief Pain Inventory (BPI)
timeFrame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
measure: Quality of life (QOL) assessed by EORTC QLQ-C30 (with BM22)
timeFrame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
measure: Toxicity as assessed by CTCAE V. 5.0
timeFrame: At follow-up MRI (1 month, 3 months, 6 months and 12 months after treatment)
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
name: Samuel Chao, MD
role: PRINCIPAL_INVESTIGATOR
References: