Image-Guided Radiosurgery or Stereotactic Body Radiation Therapy in Treating Patients With Localized Spine Metastasis

NCT ID: NCT00922974

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 399 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2020-04-06

Brief 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 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.

Conditions

Metastatic Cancer; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiosurgery/SBRT

Group Type: EXPERIMENTAL

Radiosurgery/SBRT

Intervention Type: RADIATION

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.

External Beam Radiation Therapy

Group Type: ACTIVE_COMPARATOR

External beam radiation therapy

Intervention Type: RADIATION

Single fraction dose of 8 Gy external beam radiation therapy

Interventions

External beam radiation therapy

Single fraction dose of 8 Gy external beam radiation therapy

Intervention Type: RADIATION

Radiosurgery/SBRT

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.

Intervention Type: RADIATION

Other Intervention Names

EBRT; stereotactic body radiotherapy; SRS; stereotactic radiosurgery

Eligibility Criteria

Inclusion Criteria

1. 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 .

2. Zubrod Performance Status 0-2;

3. Age ≥ 18;

4. History/physical examination within 2 weeks prior to registration;

5. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;

6. Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control;

7. 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.

8. 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.

9. 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).

10. 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.

11. Patients with a paraspinal mass ≤ 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible.

12. Patients must provide study specific informed consent prior to study entry.

Exclusion Criteria

1. Histologies of myeloma or lymphoma;

2. Non-ambulatory patients;

3. Spine instability due to a compression fracture;

4. > 50% loss of vertebral body height;

5. Frank spinal cord compression or displacement or epidural compression within 3 mm of the spinal cord;

6. Patients with rapid neurologic decline;

7. Bony retropulsion causing neurologic abnormality;

8. Prior radiation to the index spine;

9. Patients for whom an MRI of the spine is medically contraindicated;

10. Patients allergic to contrast dye used in MRIs or CT scans or who cannot be premedicated for the use of contrast dye.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Ryu, MD

Role: PRINCIPAL_INVESTIGATOR

Josephine Ford Cancer Center

Locations

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, United States

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus

New Britain, Connecticut, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

OSF St. Francis Medical Center

Peoria, Illinois, United States

Cancer Center at Ball Memorial Hospital

Muncie, Indiana, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Billings Clinic - Downtown

Billings, Montana, United States

Nebraska Medical Center

Omaha, Nebraska, United States

Payson Center for Cancer Care at Concord Hospital

Concord, New Hampshire, United States

Seacoast Cancer Center at Wentworth - Douglass Hospital

Dover, New Hampshire, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Capital Health Regional Cancer Center

Pennington, New Jersey, United States

Stony Brook University Cancer Center

Stony Brook, New York, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

UPMC - Shadyside

Pittsburgh, Pennsylvania, United States

UPMC Cancer Center at UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

All Saints Cancer Center at Wheaton Franciscan Healthcare

Racine, Wisconsin, United States

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Countries

United States; Canada; Israel

References

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.

Reference Type: RESULT

PMID: 24890347 (View on PubMed)

Ryu 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.

Reference Type: DERIVED

PMID: 37079324 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Study Documents

Document Type: Individual Participant Data Set

Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

View Document

Other Identifiers

CDR0000646803

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-01687

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG-0631

Identifier Type: -

Identifier Source: org_study_id