Metastatic CancerPhase 2/3NCT00922974
Image-Guided Radiosurgery or Stereotactic Body Radiation Therapy in Treating Patients With Localized Spine Metastasis
A Phase 2/3 study testing External beam radiation therapy and Radiosurgery/SBRT in people with Metastatic Cancer and Pain, run by Radiation Therapy Oncology Group at 38 sites in 3 countries.
Trial summary
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This randomized phase II/III trial is studying how well image-guided radiosurgery or stereotactic body radiation therapy works and compares it… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Metastatic Cancer, Pain
- What is being tested?
- External beam radiation therapy and Radiosurgery/SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 399 participants
- Where
- 38 sitesin 3 countries
- Study dates
- Nov 2009to 6 Apr 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have localized spine metastasis from the C1 to L5 levels by a screening imaging study [bone scan, positron emission tomography (PET), computerized tomography (CT), or magnetic resonance imaging (MRI)] (a solitary spine metastasis; two separate spine levels; or up to 3 separate sites [e.g., C5, T5-6, and T12] are permitted.) Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Patients can have other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible. See Figure 1 in Section 3.1.1. of the protocol for a depiction of eligible metastatic lesions: 1) a solitary spine metastasis; 2) two contiguous spine levels involved; or 3) a maximum of 3 separate sites. Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Epidural compression (arrow) is eligible when there is a ≥ 3 mm gap between the spinal cord and the edge of the epidural lesion (see #10). A paraspinal mass ≤ 5 cm is allowed (see #11).
- There can be multiple small metastatic lesions shown in other vertebral bodies as shown in referenced diagram. The metastatic lesion of each spine should be less than 20% of the vertebral body as opposed to the diffuse vertebral involvement. These small lesions are often seen in the MRI even when bone scan or PET was negative. Most of these lesions are not clinically required to be treated and are therefore not included in the target volume of this protocol. Only the painful spine (pain score≥ 5) is to be treated .
- Zubrod Performance Status 0-2;
- Age ≥ 18;
- History/physical examination within 2 weeks prior to registration;
- Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;
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- Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control;
- MRI (contrast is not required but strongly recommended) of the involved spine within 4 weeks prior to registration to determine the extent of the spine involvement; an MRI is required as it is superior to a CT scan in delineating the spinal cord as well as identifying an epidural or paraspinal soft tissue component. Note: If an MRI was done as a screening imaging study for eligibility (see Section -1), the MRI can be used as the required MRI for treatment planning.
- Numerical Rating Pain Scale within 1 week prior to registration; the patient must have a score on the Scale of ≥ 5 for at least one of the planned sites for spine radiosurgery. Documentation of the patient's initial pain score is required. Patients taking medication for pain at the time of registration are eligible.
- Neurological examination within 1 week prior to registration to rule out rapid neurologic decline; see Appendix III for the standardized neurological examination. Patients with mild to moderate neurological signs are eligible. These neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 (lower extremity for ambulation or upper extremity for raising arms and/or arm function).
- Patients with epidural compression are eligible provided that there is a ≥ 3 mm gap between the spinal cord and the edge of the epidural lesion.
- Patients with a paraspinal mass ≤ 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible.
- Patients must provide study specific informed consent prior to study entry.
Who cannot join
- Histologies of myeloma or lymphoma;
- Non-ambulatory patients;
- Spine instability due to a compression fracture;
- > 50% loss of vertebral body height;
- Frank spinal cord compression or displacement or epidural compression within 3 mm of the spinal cord;
- Patients with rapid neurologic decline;
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- Bony retropulsion causing neurologic abnormality;
- Prior radiation to the index spine;
- Patients for whom an MRI of the spine is medically contraindicated;
- Patients allergic to contrast dye used in MRIs or CT scans or who cannot be premedicated for the use of contrast dye.
Trial locations and contacts
38 sites in 3 countries.
38 sites in 3 countries
United States34 sites
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, 44309-2090
University of Colorado Cancer Center at UC Health Sciences Center
Aurora, Colorado, 80045
St. Agnes Hospital Cancer Center
Baltimore, Maryland, 21229
Billings Clinic - Downtown
Billings, Montana, 59107-7000
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, 80933
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210-1240
Payson Center for Cancer Care at Concord Hospital
Concord, New Hampshire, 03301
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
Seacoast Cancer Center at Wentworth - Douglass Hospital
Dover, New Hampshire, 03820
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, 32207
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0002
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, 40536-0093
James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
Cancer Center at Ball Memorial Hospital
Muncie, Indiana, 47303-3499
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
New Britain, Connecticut, 06050
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
Nebraska Medical Center
Omaha, Nebraska, 68198
Capital Health Regional Cancer Center
Pennington, New Jersey, 08534
OSF St. Francis Medical Center
Peoria, Illinois, 61637
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, 19107-5541
UPMC - Shadyside
Pittsburgh, Pennsylvania, 15213-2582
UPMC Cancer Center at UPMC Presbyterian
Pittsburgh, Pennsylvania, 15213
All Saints Cancer Center at Wheaton Franciscan Healthcare
Racine, Wisconsin, 53405
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, 48073
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Stony Brook University Cancer Center
Stony Brook, New York, 11794-9446
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, 19096
Canada3 sites
Hopital Notre-Dame du CHUM
Montreal, Quebec, H2L 4M1
McGill Cancer Centre at McGill University
Montreal, Quebec, H2W 1S6
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, K1Y 4E9
About this study
Official title: Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastasis
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This randomized phase II/III trial is studying how well image-guided radiosurgery or stereotactic body radiation therapy works and compares it to external-beam radiation therapy in treating patients with localized spine metastasis.
Read the detailed description
OBJECTIVES:
Primary
- Determine the feasibility of successfully delivering image-guided radiosurgery or stereotactic body radiotherapy (SBRT) in patients with spine metastases in a cooperative group setting. (Phase II)
- Determine whether image-guided radiosurgery or SBRT (single dose of 16 Gy) improves pain control as measured by the 11-point Numerical Rating Pain Scale (NRPS) compared to conventional external beam radiotherapy (single dose of 8 Gy). (Phase III)
Secondary
- Determine whether image-guided radiosurgery or SBRT improves the rapidity of pain response and increases the duration of pain response at the treated site(s) compared to conventional external beam radiotherapy, as measured by the NRPS. (Phase III)
- Compare adverse events associated with these treatment regimens, as measured by NCI CTCAE v3.0 criteria. (Phase III)
- Evaluate the long-term effects (24 months) of image-guided radiosurgery or SBRT on the vertebral bone (e.g., compression fracture) and the spinal cord, as measured by MRI. (Phase III)
DETAILS:
This is a multicenter, phase II study followed by a randomized phase III study. Patients enrolled in the phase III portion are stratified according to the number of spine metastases to be treated (1 vs 2-3) and the type of tumor (radioresistant [including soft tissue sarcomas, melanomas, and renal cell carcinomas] vs other).
Phase II patients undergo MRI of the treated spine at baseline and at 3 months; phase III patients undergo MRI at baseline and at 3, 6, 12, and 24 months. Patients enrolled in the phase III portion also complete the Numerical Rating Pain Scale at baseline, at 1, 2, and 3 weeks after randomization, and at 1, 3, 6, 12, and 24 months. Patients are followed after completion of study treatment.
- Conditions
- Metastatic Cancer, Pain
- Being tested
- External beam radiation therapy, Radiosurgery/SBRT
- Keywords
- spinal bone metastases, pain
- Medical subject headings
- Neoplasm Metastasis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External beam radiation therapyRadiation
Also called EBRT
Single fraction dose of 8 Gy external beam radiation therapy
Radiosurgery/SBRTRadiation
Also called stereotactic body radiotherapy, SRS, stereotactic radiosurgery
Single fraction dose image-guided radiosurgery / stereotactic body radiotherapy (SBRT). The phase II component uses 16 Gy. The phase III component allows 16 or 18 Gy as preferred by the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Radiosurgery/SBRT | Experimental | Not described Receives: Radiation: Radiosurgery/SBRT |
| External Beam Radiation Therapy | Active comparator | Not described Receives: Radiation: External beam radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Receiving Radiosurgery/SBRT Per Protocol or With Minor Variation (Phase II)
Treatment delivery was centrally reviewed by the study chair and medical physics co-chair. Success was defined as having a review of "per protocol" or "minor variation". A 70% success rate was required for continuation to the phase III component.
- Target volume compliance in is defined as the following levels of target coverage in reference to dose volume:
- Per protocol: ≥ 90%
- Minor variation: 80%-90%
- Major deviation: <80% of of dose volume.
- Image-Guided Radiotherapy (IGRT) compliance is defined as the following differences in IGRT images between simulation/planning and treatment, as well as at the end of treatment:
- Per protocol: <2 mm
- Minor variation: 2mm - 3mm
- Major deviation: > 3mm
Measured: The day of protocol treatment
Percentage of Patients With Complete or Partial Pain Response at 3 Months (Phase III)
Pain is measured by the Numerical Rating Pain Scale (NRPS) a numerical 11-point scale (0-10) with 0 = no pain, 1-4 = mild, 5-6 = moderate, and 7-10 = severe with 10 the worst pain imaginable. Pain response is calculated as 3 month score - baseline score with a positive value indicating increased pain and a negative value indicating decreased pain. Patients with complete or partial pain response as defined below are considered responders. The index site is the lesion with the highest baseline (day of radiosurgery) pain score. If multiple sites have the same baseline pain score, the index site is the most cephalad lesion.
- Complete response: post-treatment pain score of 0 at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s).
- Partial response: post-treatment improvement of at least 3 points at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s).
Measured: Baseline and 3 months
Secondary outcomes (9)
Percentage of Participants With Pain Response Through Two Years (Phase III)
Pain is measured by the NRPS, a numerical 11-point scale from 0=no pain to 10=worst pain imaginable. Magnitude of pain response = post-baseline score - baseline score with a positive value indicating increased pain and a negative value indicating decreased pain. Pain response begins when a patient improves at least 3 points at the index site. (Although pain medication and pain response were part of the protocol definition of pain response, they were unable to be assessed accurately during weeks 1-3 and therefore were not included in the final definition used here.) Pain response time is defined as time from randomization to the date of pain response, last known follow-up (censored), or death (censored). Rates of participants with pain response are estimated using the Kaplan-Meier method. The distributions of pain response times are compared between the arms. Two-year rates are provided.
Measured: Baseline to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
Percentage of Participants With Pain Relapse Through Two Years (Phase III)
Pain is measured by the NRPS, a numerical 11-point scale from 0=no pain to 10=worst pain imaginable. Amount of pain response = post-baseline score - baseline score with a positive value indicating increased pain and a negative value indicating decreased pain. Pain response begins when a patient improves at least 3 points at the index site. Pain response ends when when the pain score increases by 3 points (relapse). (Although pain medication and pain response were part of the protocol definition of pain response, they were unable to be assessed accurately during weeks 1-3 and therefore were not included in the final definition used here.) Pain relapse time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death (censored). Rates of participants with pain relapse are estimated using the Kaplan-Meier method. The distributions of pain relapse times are compared between the arms. Two-year rates are provided.
Measured: Randomization to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
Percentage of Patients With Adverse Events at 3 Months (Phase III)
Common Terminology Criteria for Adverse Events (version 3.0) grades adverse event (AE) severity from 1=mild to 5=death. Summary data is provided in this outcome measure.; See Adverse Events Module for specific adverse event data.
Measured: Baseline to 3 months
Percentage of Participants With a Vertebral Compression Fracture Through Two Years (Phase III)
Failure is defined as a vertebral compression fracture. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without compression fracture (competing risk). Failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared between the arms. Two-year rates are provided.
Measured: From randomization to two years.
Percentage of Participants With Spinal Cord Damage Through Two Years
Failure is defined as spinal cord damage. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without compression fracture (competing risk). Failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared between the arms. Two-year rates are provided.
Measured: From randomization to two years
Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at 3 Months (Phase III)
The FACT-G is a validated 27-item measure in which a higher score represents higher quality of life (QOL). Physical, functional, social and emotional well-being subscale scores are added together to form the FACT-G total score. Responses range from 0=Not a lot to 4=Very much. Certain items must be reversed before being added, by subtracting the response from 4. Subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Total score ranges from 0-108; physical, social and functional subscales from 0-28; emotional subscale from 0-24. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing the subscale scores can be prorated. Change at 3 months is calculated as 3 month score - baseline score with a positive change indicating improvement in QOL.
Measured: Baseline and 3 months
Change in Brief Pain Inventory (BPI) Worst Pain Score Through Two Years (Phase III)
The Brief Pain Inventory Worst Pain score measures self-reported worst pain in the last week. Possible scores range from 0 (no pain) to 10 (worst pain imaginable), with higher scores indicating a worse outcome. Change is calculated as baseline score subtracted from post-baseline score with a positive change indicating more pain.
Measured: Baseline, 3, 6, 12, and 24 months
Change in EuroQol 5 Dimension (EQ-5D) Index Score Through Two Years (Phase III)
The EQ-5D index score measures health status. Possible scores range from 0 (worst health state) to 1 (best health state), with higher scores indicating better health. Change is calculated as baseline score subtracted from post-baseline score with a positive change indicating improved health status.
Measured: Baseline, 3, 6, 12, and 24 months
Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score Through Two Years (Phase III)
The FACT-G total score gives a combined score of the four domains of health-related quality of life (HRQOL) in cancer patients: Physical, social, emotional, and functional well-being. Possible total scores range from 0 to 108 with higher scores indicating a better HRQOL. Change is calculated as baseline score subtracted from post-baseline score with a positive change indicating improvement in HRQOL.
Measured: Baseline, 3, 6, 12, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study startNov 2009
- Primary completionJan 2018
- Study completion6 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 399 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radiation Therapy Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Samuel Ryu, MD, Principal investigator, Josephine Ford Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00922974
- Sponsor's protocol ID
- RTOG-0631
- Other IDs
- CDR0000646803, NCI-2009-01687
- Status last verified
- Apr 2021
- First submitted
- 17 Jun 2009
- Last updated
- 29 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ, Movsas B, Kanner AA, Berk LB, Followill DS, Kachnic LA. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol. 2014 Mar-Apr;4(2):76-81. doi: 10.1016/j.prro.2013.05.001. Epub 2013 Jun 4.
PubMed 24890347Ryu S, Deshmukh S, Timmerman RD, Movsas B, Gerszten P, Yin FF, Dicker A, Abraham CD, Zhong J, Shiao SL, Tuli R, Desai A, Mell LK, Iyengar P, Hitchcock YJ, Allen AM, Burton S, Brown D, Sharp HJ, Dunlap NE, Siddiqui MS, Chen TH, Pugh SL, Kachnic LA. Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. JAMA Oncol. 2023 Jun 1;9(6):800-807. doi: 10.1001/jamaoncol.2023.0356.
PubMed 37079324
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastasis
- ClinicalTrials.gov ID
- NCT00922974
- Acronym / sponsor ID
- RTOG-0631
- Conditions
- Metastatic Cancer, Pain
- Keywords
- spinal bone metastases, pain
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 399 participants (actual)
- Lead sponsor
- Radiation Therapy Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Study start
- Nov 2009 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- 6 Apr 2020 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 16 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This randomized phase II/III trial is studying how well image-guided radiosurgery or stereotactic body radiation therapy works and compares it to external-beam radiation therapy in treating patients with localized spine metastasis.
Detailed description
OBJECTIVES:
Primary
- Determine the feasibility of successfully delivering image-guided radiosurgery or stereotactic body radiotherapy (SBRT) in patients with spine metastases in a cooperative group setting. (Phase II)
- Determine whether image-guided radiosurgery or SBRT (single dose of 16 Gy) improves pain control as measured by the 11-point Numerical Rating Pain Scale (NRPS) compared to conventional external beam radiotherapy (single dose of 8 Gy). (Phase III)
Secondary
- Determine whether image-guided radiosurgery or SBRT improves the rapidity of pain response and increases the duration of pain response at the treated site(s) compared to conventional external beam radiotherapy, as measured by the NRPS. (Phase III)
- Compare adverse events associated with these treatment regimens, as measured by NCI CTCAE v3.0 criteria. (Phase III)
- Evaluate the long-term effects (24 months) of image-guided radiosurgery or SBRT on the vertebral bone (e.g., compression fracture) and the spinal cord, as measured by MRI. (Phase III)
DETAILS:
This is a multicenter, phase II study followed by a randomized phase III study. Patients enrolled in the phase III portion are stratified according to the number of spine metastases to be treated (1 vs 2-3) and the type of tumor (radioresistant [including soft tissue sarcomas, melanomas, and renal cell carcinomas] vs other).
Phase II patients undergo MRI of the treated spine at baseline and at 3 months; phase III patients undergo MRI at baseline and at 3, 6, 12, and 24 months. Patients enrolled in the phase III portion also complete the Numerical Rating Pain Scale at baseline, at 1, 2, and 3 weeks after randomization, and at 1, 3, 6, 12, and 24 months. Patients are followed after completion of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiosurgery/SBRT | Experimental | Radiation: Radiosurgery/SBRT |
| External Beam Radiation Therapy | Active comparator | Radiation: External beam radiation therapy |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- The patient must have localized spine metastasis from the C1 to L5 levels by a screening imaging study [bone scan, positron emission tomography (PET), computerized tomography (CT), or magnetic resonance imaging (MRI)] (a solitary spine metastasis; two separate spine levels; or up to 3 separate sites [e.g., C5, T5-6, and T12] are permitted.) Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Patients can have other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible. See Figure 1 in Section 3.1.1. of the protocol for a depiction of eligible metastatic lesions: 1) a solitary spine metastasis; 2) two contiguous spine levels involved; or 3) a maximum of 3 separate sites. Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Epidural compression (arrow) is eligible when there is a ≥ 3 mm gap between the spinal cord and the edge of the epidural lesion (see #10). A paraspinal mass ≤ 5 cm is allowed (see #11).
- Zubrod Performance Status 0-2;
- Age ≥ 18;
- History/physical examination within 2 weeks prior to registration;
- Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;
Key exclusion criteria (10 listed)
- Histologies of myeloma or lymphoma;
- Non-ambulatory patients;
- Spine instability due to a compression fracture;
- > 50% loss of vertebral body height;
- Frank spinal cord compression or displacement or epidural compression within 3 mm of the spinal cord;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| External beam radiation therapyAlso: EBRTSingle fraction dose of 8 Gy external beam radiation therapy | Radiation | External Beam Radiation Therapy |
| Radiosurgery/SBRTAlso: stereotactic body radiotherapy, SRS, stereotactic radiosurgerySingle fraction dose image-guided radiosurgery / stereotactic body radiotherapy (SBRT). The phase II component uses 16 Gy. The phase III component allows 16 or 18 Gy as preferred by the treating physician. | Radiation | Radiosurgery/SBRT |
Primary outcome
Percentage of Patients Receiving Radiosurgery/SBRT Per Protocol or With Minor Variation (Phase II)
Time frame: The day of protocol treatment
Treatment delivery was centrally reviewed by the study chair and medical physics co-chair. Success was defined as having a review of "per protocol" or "minor variation". A 70% success rate was required for continuation to the phase III component. * Target volume compliance in is defined as the following levels of target coverage in reference to dose volume: * Per protocol: ≥ 90% * Minor variation: 80%-90% * Major deviation: <80% of of dose volume. * Image-Guided Radiotherapy (IGRT) compliance is defined as the following differences in IGRT images between simulation/planning and treatment, as well as at the end of treatment: * Per protocol: <2 mm * Minor variation: 2mm - 3mm * Major deviation: > 3mm
Percentage of Patients With Complete or Partial Pain Response at 3 Months (Phase III)
Time frame: Baseline and 3 months
Pain is measured by the Numerical Rating Pain Scale (NRPS) a numerical 11-point scale (0-10) with 0 = no pain, 1-4 = mild, 5-6 = moderate, and 7-10 = severe with 10 the worst pain imaginable. Pain response is calculated as 3 month score - baseline score with a positive value indicating increased pain and a negative value indicating decreased pain. Patients with complete or partial pain response as defined below are considered responders. The index site is the lesion with the highest baseline (day of radiosurgery) pain score. If multiple sites have the same baseline pain score, the index site is the most cephalad lesion. * Complete response: post-treatment pain score of 0 at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s). * Partial response: post-treatment improvement of at least 3 points at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s).
9 secondary outcomes
Percentage of Participants With Pain Response Through Two Years (Phase III)
Time frame: Baseline to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
Percentage of Participants With Pain Relapse Through Two Years (Phase III)
Time frame: Randomization to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
Percentage of Patients With Adverse Events at 3 Months (Phase III)
Time frame: Baseline to 3 months
Percentage of Participants With a Vertebral Compression Fracture Through Two Years (Phase III)
Time frame: From randomization to two years.
Percentage of Participants With Spinal Cord Damage Through Two Years
Time frame: From randomization to two years
Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at 3 Months (Phase III)
Time frame: Baseline and 3 months
Change in Brief Pain Inventory (BPI) Worst Pain Score Through Two Years (Phase III)
Time frame: Baseline, 3, 6, 12, and 24 months
Change in EuroQol 5 Dimension (EQ-5D) Index Score Through Two Years (Phase III)
Time frame: Baseline, 3, 6, 12, and 24 months
Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score Through Two Years (Phase III)
Time frame: Baseline, 3, 6, 12, and 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24890347Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ, Movsas B, Kanner AA, Berk LB, Followill DS, Kachnic LA. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol. 2014 Mar-Apr;4(2):76-81. doi: 10.1016/j.prro.2013.05.001. Epub 2013 Jun 4.
- Derived from this study: PubMed 37079324Ryu S, Deshmukh S, Timmerman RD, Movsas B, Gerszten P, Yin FF, Dicker A, Abraham CD, Zhong J, Shiao SL, Tuli R, Desai A, Mell LK, Iyengar P, Hitchcock YJ, Allen AM, Burton S, Brown D, Sharp HJ, Dunlap NE, Siddiqui MS, Chen TH, Pugh SL, Kachnic LA. Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. JAMA Oncol. 2023 Jun 1;9(6):800-807. doi: 10.1001/jamaoncol.2023.0356.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Ryu, MD principal investigator
Josephine Ford Cancer Center
38 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing External beam radiation therapy and Radiosurgery/SBRT in people with Metastatic Cancer and Pain, run by Radiation Therapy Oncology Group at 38 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients Receiving Radiosurgery/SBRT Per Protocol or With Minor Variation (Phase II) (time frame: The day of protocol treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00922974, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.