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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04218617
Recruitment Status : Recruiting
First Posted : January 6, 2020
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

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.


Condition or disease Intervention/treatment Phase
Spine Metastases Spine Stereotactic Radiosurgery (sSRS) Device: Diagnostic MRI Device: Planning MRI Other: Simulation CT Other: QOL assessment Other: Brief pain inventory (BPI) Radiation: sSRS in 1 fraction Radiation: sSRS in 2 fraction Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases
Actual Study Start Date : February 7, 2020
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : January 1, 2024

Arm Intervention/treatment
Experimental: Arm 1 - Single fraction
sSRS 18 Gy in 1 fraction
Device: Diagnostic MRI
Diagnostic MRI

Device: Planning MRI
Planning MRI: high definition (HD) MRI of the region of interest (1 vertebral level above and below the level(s) being treated)

Other: Simulation CT
Simulation CT is obtained (1.5 mm slice thickness)

Other: QOL assessment
QOL assessment

Other: Brief pain inventory (BPI)
Brief pain inventory (BPI), including narcotic assessment

Radiation: sSRS in 1 fraction
sSRS 18 Gy in 1 fraction

Active Comparator: Arm 2 - Two fraction
sSRS 24 Gy in 2 fractions
Device: Diagnostic MRI
Diagnostic MRI

Device: Planning MRI
Planning MRI: high definition (HD) MRI of the region of interest (1 vertebral level above and below the level(s) being treated)

Other: Simulation CT
Simulation CT is obtained (1.5 mm slice thickness)

Other: QOL assessment
QOL assessment

Other: Brief pain inventory (BPI)
Brief pain inventory (BPI), including narcotic assessment

Radiation: sSRS in 2 fraction
sSRS 24 Gy in 2 fractions to be delivered either on consecutive days or one day apart.




Primary Outcome Measures :
  1. 6-month cumulative incidence of Vertebral Compression Fracture (VCF) associated with single- and two-fraction sSRS [ Time Frame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment) ]

    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 :
  1. 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 [ Time Frame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment) ]

    LC as defined as absence of local progression of disease, which include the following:

    1. Gross unequivocal increase in tumor volume or linear dimension.
    2. Any new or progressive tumor within the epidural space.
    3. Neurologic deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease dimensions on MRI.

  2. Pain control (PC) as assessed by the Brief Pain Inventory (BPI) [ Time Frame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment) ]

    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.


  3. Quality of life (QOL) assessed by EORTC QLQ-C30 (with BM22) [ Time Frame: At baseline and for each subsequent follow-up MRI (at 1 month, 3 months, 6 months and 12 months after treatment) ]
    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")

  4. Toxicity as assessed by CTCAE V. 5.0 [ Time Frame: At follow-up MRI (1 month, 3 months, 6 months and 12 months after treatment) ]

    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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04218617


Contacts
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Contact: Samuel T Chao, MD 1-866-223-8100 TaussigResearch@ccf.org
Contact: Ehsan Balagamwala, MD 1-866-223-8100 balagae@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Samuel T. Chao, MD    866-223-8100    TaussigResearch@ccf.org   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
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Principal Investigator: Samuel Chao, MD Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
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Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT04218617    
Other Study ID Numbers: CASE3319
First Posted: January 6, 2020    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in publication, after de-identification
Time Frame: 1 year after last participant is enrolled. Data will be available for a total of 2 years
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).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Case Comprehensive Cancer Center:
C79.40
C79.49
C79.51
C79.52
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes