Stereotactic Radiosurgery in Treating Patients With Spinal Metastases

Cyberknife Radiosurgery for Improving Palliation of Metastatic Tumors of the Spine

RATIONALE: Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. It may also help patients with spinal metastases live more comfortably.

PURPOSE: This phase I trial is studying the side effects and best dose of stereotactic radiosurgery in treating patients with spinal metastases.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer
• Intervention / Treatment: Other: questionnaire administration; Procedure: diffusion tensor imaging; Procedure: functional magnetic resonance imaging; Radiation: single-fraction SRS; Radiation: hypo-fractionated SRS

Detailed Description

OBJECTIVES:

• To implement CyberKnife® technology for improving palliation in patients with spinal metastases.
• To determine the maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery in these patients.
• To evaluate functional and diffusion MRI parameters in the spinal cord and tumor after treatment with Cyberknife® radiosurgery.

OUTLINE: Patients undergo placement of gold fiducial markers at the time of open surgical resection or percutaneous needle biopsy. Patients then undergo CyberKnife® hypofractionated stereotactic radiosurgery over 30-90 minutes daily for 2-3 days.

Patients undergo functional MRI and diffusion tensor imaging at baseline and then at 6 weeks and 6 months after completion of treatment. Patients also complete a pain questionnaire at baseline and then at 3, 6, 9, 12, 18, and 24 months after completion of treatment.

After completion of study treatment, patients are followed periodically for up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic spinal tumor

  • Localized spinal metastasis, defined as one of the following:

    • Solitary spinal metastasis

    • Two contiguous spinal levels

      • No more than 2 adjacent spinal levels involved by a single tumor
    • Involvement of ≤ 3 separate sites (e.g., C5, T5, and T12)
  • Tumor size ≤ 5 cm

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 6 months
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be ambulatory

Exclusion Criteria:

• Not pregnant or nursing
• No spinal instability
• No rapid neurological decline
• No bony retropulsions causing neurological abnormalities
• No total paraplegia for > 48 hours
• No psychological issues that would preclude completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior treatment for spinal tumor that would result in potential overlap of radiotherapy fields
• No treatment that is expected to exceed spinal cord tolerance or other regional normal tissue tolerance
• No tumors that are exquisitely radiosensitive and controlled with conventional radiotherapy (e.g., lymphoma, leukemia, multiple myeloma, or germ cell tumors)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-fraction radiosurgery; 16 Gray; Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 16 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: single-fraction SRS; two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy
Experimental: Hypo-fractionated radiosurgery; 21 Gray; Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 21 Gray	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: hypo-fractionated SRS; two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy
Experimental: Single-fraction radiosurgery; 18 Gray; Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 18 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: single-fraction SRS; two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy
Experimental: Single-fraction radiosurgery; 20 Gray; Subjects able to achieve the spinal cord dose constraints for single-fraction SRS stereotactic radiosurgery Radiation: stereotactic radiotherapy at 20 Gray Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: single-fraction SRS; two to three consecutive daily sessions within one week for 3 cohorts- for 3 cohorts- Cohort 1 = 16 Gy; Cohort 2 = 18 Gy; Cohort 3 = 20 Gy
Experimental: Hypo-fractionated radiosurgery; 24 Gray; Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 24 Gray	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: hypo-fractionated SRS; two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy
Experimental: Hypo-fractionated radiosurgery; 27 Gray; Subjects unable to achieve the spinal cord dose constraints for single-fraction radiosurgery (SRS), based on tumor location and expected tolerance dose to the adjacent normal tissue, will be offered hypo-fractionated SRS (3 fractions) Radiation: stereotactic radiotherapy Questionnaire administration diffusion tensor imaging functional magnetic resonance imaging hypo-fractionated radiation therapy at 27 Gray	Other: questionnaire administration; prior to radiosurgery, at radiosurgery completion, and then at subsequent follow-ups (3, 6, 9, 12, 18, and 24 months after treatment; Procedure: diffusion tensor imaging; prior to initiating CyberKnife radiosurgery, at 6 weeks after CyberKnife therapy, and at 6 months after CyberKnife therapy; Procedure: functional magnetic resonance imaging; prior to CyberKnife, at 6 weeks, and 3 months after CyberKnife?, every 3 months for the first year, and every 6 months thereafter; Radiation: hypo-fractionated SRS; two to three consecutive daily sessions within one week for 3 cohorts- Cohort 1 = 21 Gy; Cohort 2 = 24 Gy; Cohort 3 = 27 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose - single fraction	Maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery	6 weeks
Maximum tolerated dose - hypofraction	Maximum tolerated dose of CyberKnife® hypofractionated stereotactic radiosurgery	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pain	Pain as measured by the Brief Pain Inventory and Roland scale	baseline and then at 3, 6, 9, 12, 18, and 24 months after completion of treatment
Spinal cord response	Spinal cord response as measured by functional MRI	baseline and then at 6 weeks and 6 months after completion of treatment

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Minh-Tam Truong, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: spinal cord metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: H-26577; W81XWH-07-1-0342 (Other Grant/Funding Number: Dept of Defense); CDR0000635267 (Other Identifier: BUMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes