Clinical trial NCT00922974: Image-Guided Radiosurgery or Stereotactic Body Radiation Therapy in Treating Patients With Localized Spine Metastasis
Official title: Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Metastatic Cancer
Pain
Keywords: spinal bone metastases
pain
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2009-06-18
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Patients Receiving Radiosurgery/SBRT Per Protocol or With Minor Variation (Phase II)
timeFrame: The day of protocol treatment
measure: Percentage of Patients With Complete or Partial Pain Response at 3 Months (Phase III)
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Percentage of Participants With Pain Response Through Two Years (Phase III)
timeFrame: Baseline to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
measure: Percentage of Participants With Pain Relapse Through Two Years (Phase III)
timeFrame: Randomization to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.
measure: Percentage of Patients With Adverse Events at 3 Months (Phase III)
timeFrame: Baseline to 3 months
measure: Percentage of Participants With a Vertebral Compression Fracture Through Two Years (Phase III)
timeFrame: From randomization to two years.
measure: Percentage of Participants With Spinal Cord Damage Through Two Years
timeFrame: From randomization to two years
measure: Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at 3 Months (Phase III)
timeFrame: Baseline and 3 months
measure: Change in Brief Pain Inventory (BPI) Worst Pain Score Through Two Years (Phase III)
timeFrame: Baseline, 3, 6, 12, and 24 months
measure: Change in EuroQol 5 Dimension (EQ-5D) Index Score Through Two Years (Phase III)
timeFrame: Baseline, 3, 6, 12, and 24 months
measure: Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score Through Two Years (Phase III)
timeFrame: Baseline, 3, 6, 12, and 24 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: New Britain
country: United States
facility: George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
state: Connecticut
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Concord
country: United States
facility: Payson Center for Cancer Care at Concord Hospital
state: New Hampshire
city: Dover
country: United States
facility: Seacoast Cancer Center at Wentworth - Douglass Hospital
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Pennington
country: United States
facility: Capital Health Regional Cancer Center
state: New Jersey
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Presbyterian
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at Wheaton Franciscan Healthcare
state: Wisconsin
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: Josephine Ford Cancer Center
name: Samuel Ryu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.