search
Back to results

Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases

Primary Purpose

Spine Metastases, Spine Stereotactic Radiosurgery (sSRS)

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Diagnostic MRI
Planning MRI
Simulation CT
QOL assessment
Brief pain inventory (BPI)
sSRS in 1 fraction
sSRS in 2 fraction
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spine Metastases focused on measuring C79.40, C79.49, C79.51, C79.52

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1 - Single fraction

Arm 2 - Two fraction

Arm Description

sSRS 18 Gy in 1 fraction

sSRS 24 Gy in 2 fractions

Outcomes

Primary Outcome Measures

6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS
6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS Each treated vertebra will be assessed individually for VCF during radiologic follow-up

Secondary Outcome Measures

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
LC as defined as absence of local progression of disease, which include the following: Gross unequivocal increase in tumor volume or linear dimension. Any new or progressive tumor within the epidural space. Neurologic deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease dimensions on MRI.
Pain control (PC) as assessed by the Brief Pain Inventory (BPI)
PC at each treated vertebral level assessed by the BPI [9 item questionnaire (range: 0-10), higher scores = worse pain], then defined by RTOG 0631 as follows: Complete relief (CR): Pain score of 0 at index site 3 mo post-treatment. CR is requisite of no increase in narcotic analgesics. Partial relief (PR): Reduction in BPI of ≥ 3 points at index site, provided other treated lesions have increased in pain score and participant did not require increase in narcotic analgesics for site of interest. Participants needing increase in narcotics for site will not be scored as having PR. Those needing increase in narcotics for a distant site will remain eligible for CR/PR. Stable response (SR): Post-treatment pain score same as or within 2 points of baseline score at index site with no increase in narcotic analgesics for site of interest. Progressive pain: Post-treatment increase of at least 3 points from baseline pain score at index site or increase in narcotics for site of interest.
Quality of life (QOL) assessed by EORTC QLQ-C30 (with BM22)
Quality of life as measured by (EORTC QOL-C30) - 30 items that are grouped into five scales functional (physical, social, emotional functioning, cognitive and role), three scales of symptoms (fatigue, pain, nausea and vomiting), a global scale of health / quality of life and a number of related individual items with the symptoms of the disease and its treatment, as well as an item of economic impact. The answers to the items on the scales refer to "last week," except the patient's physical functioning scale whose time frame is the present. These answers obey a Likert format, which ranges from 1 ("Not at all") and 4 ("A lot")
Toxicity as assessed by CTCAE V. 5.0
Toxicity as assessed by criteria in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Rates of grade 1-5 toxicities will be reported

Full Information

First Posted
January 2, 2020
Last Updated
July 5, 2023
Sponsor
Case Comprehensive Cancer Center
search

1. Study Identification

Unique Protocol Identification Number
NCT04218617
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spine Metastases, Spine Stereotactic Radiosurgery (sSRS)
Keywords
C79.40, C79.49, C79.51, C79.52

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 - Single fraction
Arm Type
Experimental
Arm Description
sSRS 18 Gy in 1 fraction
Arm Title
Arm 2 - Two fraction
Arm Type
Active Comparator
Arm Description
sSRS 24 Gy in 2 fractions
Intervention Type
Device
Intervention Name(s)
Diagnostic MRI
Intervention Description
Diagnostic MRI
Intervention Type
Device
Intervention Name(s)
Planning MRI
Intervention Description
Planning MRI: high definition (HD) MRI of the region of interest (1 vertebral level above and below the level(s) being treated)
Intervention Type
Other
Intervention Name(s)
Simulation CT
Intervention Description
Simulation CT is obtained (1.5 mm slice thickness)
Intervention Type
Other
Intervention Name(s)
QOL assessment
Intervention Description
QOL assessment
Intervention Type
Other
Intervention Name(s)
Brief pain inventory (BPI)
Intervention Description
Brief pain inventory (BPI), including narcotic assessment
Intervention Type
Radiation
Intervention Name(s)
sSRS in 1 fraction
Intervention Description
sSRS 18 Gy in 1 fraction
Intervention Type
Radiation
Intervention Name(s)
sSRS in 2 fraction
Intervention Description
sSRS 24 Gy in 2 fractions to be delivered either on consecutive days or one day apart.
Primary Outcome Measure Information:
Title
6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS
Description
6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS Each treated vertebra will be assessed individually for VCF during radiologic follow-up
Time Frame
At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
Secondary Outcome Measure Information:
Title
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
Description
LC as defined as absence of local progression of disease, which include the following: Gross unequivocal increase in tumor volume or linear dimension. Any new or progressive tumor within the epidural space. Neurologic deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease dimensions on MRI.
Time Frame
At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
Title
Pain control (PC) as assessed by the Brief Pain Inventory (BPI)
Description
PC at each treated vertebral level assessed by the BPI [9 item questionnaire (range: 0-10), higher scores = worse pain], then defined by RTOG 0631 as follows: Complete relief (CR): Pain score of 0 at index site 3 mo post-treatment. CR is requisite of no increase in narcotic analgesics. Partial relief (PR): Reduction in BPI of ≥ 3 points at index site, provided other treated lesions have increased in pain score and participant did not require increase in narcotic analgesics for site of interest. Participants needing increase in narcotics for site will not be scored as having PR. Those needing increase in narcotics for a distant site will remain eligible for CR/PR. Stable response (SR): Post-treatment pain score same as or within 2 points of baseline score at index site with no increase in narcotic analgesics for site of interest. Progressive pain: Post-treatment increase of at least 3 points from baseline pain score at index site or increase in narcotics for site of interest.
Time Frame
At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
Title
Quality of life (QOL) assessed by EORTC QLQ-C30 (with BM22)
Description
Quality of life as measured by (EORTC QOL-C30) - 30 items that are grouped into five scales functional (physical, social, emotional functioning, cognitive and role), three scales of symptoms (fatigue, pain, nausea and vomiting), a global scale of health / quality of life and a number of related individual items with the symptoms of the disease and its treatment, as well as an item of economic impact. The answers to the items on the scales refer to "last week," except the patient's physical functioning scale whose time frame is the present. These answers obey a Likert format, which ranges from 1 ("Not at all") and 4 ("A lot")
Time Frame
At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment)
Title
Toxicity as assessed by CTCAE V. 5.0
Description
Toxicity as assessed by criteria in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Rates of grade 1-5 toxicities will be reported
Time Frame
At follow-up MRI (1 month, 3 months, 6 months and 12 months after treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Samuel T Chao, MD
Phone
1-866-223-8100
Email
TaussigResearch@ccf.org
First Name & Middle Initial & Last Name or Official Title & Degree
Ehsan Balagamwala, MD
Phone
1-866-223-8100
Email
balagae@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Chao, MD
Organizational Affiliation
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samuel T. Chao, MD
Phone
866-223-8100
Email
TaussigResearch@ccf.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in publication, after de-identification
IPD Sharing Time Frame
1 year after last participant is enrolled. Data will be available for a total of 2 years
IPD Sharing Access Criteria
Investigators whose purposed use of the data has been approved by the Cleveland Clinic Independent Review Committee. Data will be provided for individual participant meta-analysis. All requests must be made in writing to Sam Chao, MD (Chaos@ccf.org) or Ehsan Balagamwala (Balagae@ccf.org).

Learn more about this trial

Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases

We'll reach out to this number within 24 hrs