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

NCT00922974 | Completed Phase 2 Results DMC

• 3 other identifiers: RTOG-0631CDR0000646803NCI-2009-01687
• Study Type: interventional
• Target: 399
• Locations: 3 countries
• Sites: 38

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.

Conditions

Metastatic Cancer; Pain

Keywords

spinal bone metastases; pain

Outcome Measures

Primary Outcomes (2)

• 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

  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).

  Baseline and 3 months

Secondary Outcomes (9)

• Percentage of Participants With Pain Response Through Two Years (Phase III)

  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)

  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)

  Baseline to 3 months

• Percentage of Participants With a Vertebral Compression Fracture Through Two Years (Phase III)

  From randomization to two years.

• Percentage of Participants With Spinal Cord Damage Through Two Years

  From randomization to two years

Study Arms (2)

Radiosurgery/SBRT

EXPERIMENTAL

Radiation: Radiosurgery/SBRT

External Beam Radiation Therapy

ACTIVE COMPARATOR

Radiation: External beam radiation therapy

Interventions

External beam radiation therapy RADIATION

Single fraction dose of 8 Gy external beam radiation therapy

Also known as: EBRT

External Beam Radiation Therapy

Radiosurgery/SBRT 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.

Also known as: stereotactic body radiotherapy, SRS, stereotactic radiosurgery

Radiosurgery/SBRT

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (38)

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

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

New Britain, Connecticut, 06050, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Cancer Center at Ball Memorial Hospital

Muncie, Indiana, 47303-3499, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

St. Agnes Hospital Cancer Center

Baltimore, Maryland, 21229, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, 48073, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Payson Center for Cancer Care at Concord Hospital

Concord, New Hampshire, 03301, United States

Location

Seacoast Cancer Center at Wentworth - Douglass Hospital

Dover, New Hampshire, 03820, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Capital Health Regional Cancer Center

Pennington, New Jersey, 08534, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

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

Columbus, Ohio, 43210-1240, United States

Location

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

Hershey, Pennsylvania, 17033-0850, United States

Location

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, 19107-5541, United States

Location

UPMC - Shadyside

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

UPMC Cancer Center at UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

All Saints Cancer Center at Wheaton Franciscan Healthcare

Racine, Wisconsin, 53405, United States

Location

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Related Publications (2)

• 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.

  PMID: 24890347 RESULT

• 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.

  PMID: 37079324 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Pain

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Samuel Ryu, MD

  Josephine Ford Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: November 1, 2009
• Primary Completion: January 1, 2018
• Study Completion: April 6, 2020
• Last Updated: April 29, 2025
• Results First Posted: May 16, 2019

Record last verified: 2021-04

Locations

IL (1); US (34); CA (3)