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Single Versus Multiple Fractionated SSRS for Spinal Metastases

Primary Purpose

Secondary Malignant Neoplasm of Spine

Status

Unknown status

Phase

Not Applicable

Locations

Taiwan

Study Type

Interventional

Intervention

SF-SSRS

MF-SSRS

About this trial

This is an interventional treatment trial for Secondary Malignant Neoplasm of Spine focused on measuring stereotactic ablative radiotherapy, spine metastasis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

To be eligible for inclusion, patients must fulfill the following criteria:

Patients with a histologic diagnosis of non-hematopoietic malignancy
Radiographic evidence of localized spine metastases without leptomeningeal involvement or intramedullary lesion
Maximum three separate sites with a maximal involvement of two continuous vertebral levels
Patients do not have prior radiotherapy to the index spine(s)
Patients with metastatic epidural spinal cord compression (≥ grade 2) at the index spine(s) who will not be treated with spine surgery after evaluation by neurosurgeon or orthopedic doctor
Age ≥ 20 years
Karnofsky performance status (KPS) ≥ 60%.
Life expectancy of ≥ 4 month.
Women of childbearing potential and male participants must practice adequate contraception
Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent

Exclusion criteria Patients fulfill any of the following criteria will be excluded from this trial

Prior radiotherapy to the index spine(s)
Serum creatinine > 2.0 mg/dL within 90 days prior registration
Contraindication to MRI such as implanted metal devices or foreign bodies, severe claustrophobia
Patients with leptomeningeal involvement or intramedullary metastasis
Inability to tolerate treatment procedure
Bony retropulsion causing neurologic abnormality
Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
- Uncontrolled active infection requiring intravenous antibiotics at the time of registration
- Transmural myocardial infarction ≤ 6 months prior to registration
- Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
- Life-threatening uncontrolled clinically significant cardiac arrhythmias
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Uncontrolled psychiatric disorder
Will receive any other investigational agent or chemotherapy and/or target therapies during treatment
Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic

Sites / Locations

National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

SF-SSRS

MF-SSRS

Arm Description

Single-Fraction (SF) Stereotactic Spine Radiosurgery

Multiple-Fraction (MF) Stereotactic Spine Radiosurgery

Outcomes

Primary Outcome Measures

Common Toxicity Criteria for Adverse Events version 4 Grade 3 or higher adverse events related to spine radiosurgery

The rate of 4-month Common Toxicity Criteria for Adverse Events version 4 grade 3 or higher adverse events definitely, probably or possibly related to treatment

Secondary Outcome Measures

The pain response rate at the treated index site(s) at 4 months by the numerical rating pain scale

Health-related quality of life for palliative cancer care patients

European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire module and Quality of Life questionnaire for palliation

Local control rate at the treated index site(s)

Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)

Late toxicity (Common Toxicity Criteria for Adverse Events version 4)

Changes of spinal cord function by Frankel's classification grading system for spine injury at 4 months

Tumor-related spinal instability by the Spinal Instability Neoplastic Score (SINS) at 4 months.

Osseous changes of the treated index site(s) on CT scan within 12 months

Full Information

NCT ID

NCT02608866

First Posted

November 13, 2015

Last Updated

July 17, 2019

Sponsor

National Taiwan University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02608866

Brief Title

Single Versus Multiple Fractionated SSRS for Spinal Metastases

Official Title

A Prospective Randomized Clinical Trial of Single Versus Multiple Fractionated Stereotactic Spine Radiosurgery for Patients With Spinal Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Unknown status

Study Start Date

November 16, 2015 (Actual)

Primary Completion Date

August 2019 (Anticipated)

Study Completion Date

August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Taiwan University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The investigators proposed this randomized study to determine the feasibility of delivering single-fraction 16-Gy versus 3-fraction 24-Gy toward spine metastatic lesion and to evaluate their toxicity profiles. The investigators' analysis will provide robust data as well as predictive factors regarding the outcome after SSRS.

Detailed Description

Although conventionally fractionated radiation therapy has been utilized for decades, the rates of complete pain relief and local control for complex tumors are sub-optimal. The management of patients with spine metastasis has undergone a great deal of change in the past 5 years. Improvements in neuroimaging, computer-assisted treatment planning, and radiation therapy techniques have led to the development of extracranial radiosurgery. SSRS is rapidly being adopted in the clinic as preliminary applications of SSRS appears promising. However, the role of SSRS remains in its infancy and lacked high-quality evidence about the treatment schedule and lacked a solid understanding of the adverse events. The Radiation Therapy Oncology Group (RTOG) 0631 phase 2/3 study was initiated to determine whether a more intensive radiation dose delivered by image guided 16-Gy dose single fraction SRS could improve pain control and quality of life as compared with conventional external-beam radiotherapy in patients with localized spine metastases . While other group used treatment schedule in a total dose of 27-30 Gy in three fractions. Serious adverse events such as vertebral compression fracture (VCF) is a fairly low-risk adverse event after conventional radiotherapy, nevertheless, the crude risk estimates for VCF after spinal stereotactic body radiation therapy is relative more frequent. Previous reports has raised the caution about the given dose and predictive factors, however; whether these two most widely used SSRS schedule (ie. single fraction versus three fractions) provide equivalent pain control and minimal side effects remained to be answered. There was no randomized trials to assess the SSRS treatment response and SSRS induced grade 3 or higher adverse events between the two most widely adopted scheme. Thus, the investigators proposed the randomized study to determine the feasibility of delivering a single 16-Gy SRS dose versus 3 fractions 24-Gy SRS dose and tried to evaluate the toxicity profile and gain robust data as well as predictive factors regarding the risk of complications after SSRS, including VCF. The investigators will incorporate the recently developed and reported reliable Spinal Instability Neoplastic Scoring (SINS) system and well-designed patient reported outcome measures (PROMs) into the protocol to predict the adverse event and quality of life of each participant. The researchers also tried to investigate the possible associations of the potential bone biomarkers for the risk assessment of SSRS-related adverse bone events. Since the patients were randomized for treatment arms, the effectiveness of SSRS treatment scheme and adverse profile can be investigated more properly in the present study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary Malignant Neoplasm of Spine

Keywords

stereotactic ablative radiotherapy, spine metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

68 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SF-SSRS

Arm Type

Experimental

Arm Description

Single-Fraction (SF) Stereotactic Spine Radiosurgery

Arm Title

MF-SSRS

Arm Type

Experimental

Arm Description

Multiple-Fraction (MF) Stereotactic Spine Radiosurgery

Intervention Type

Radiation

Intervention Name(s)

SF-SSRS

Intervention Description

Spine stereotactic radiosurgery/ablative radiotherapy (SSRS) with 16 Gy in single fraction to the defined target volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc).

Intervention Type

Radiation

Intervention Name(s)

MF-SSRS

Intervention Description

SSRS with 24 Gy in three fractions to the defined target volume using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc). Treatment should be given on every other day. Treatment on the consecutive days to the same target volume is not allowed.

Primary Outcome Measure Information:

Title

Common Toxicity Criteria for Adverse Events version 4 Grade 3 or higher adverse events related to spine radiosurgery

Description

The rate of 4-month Common Toxicity Criteria for Adverse Events version 4 grade 3 or higher adverse events definitely, probably or possibly related to treatment

Time Frame

16 weeks after SSRS

Secondary Outcome Measure Information:

Title

The pain response rate at the treated index site(s) at 4 months by the numerical rating pain scale

Time Frame

16 weeks after Stereotactic Spine Radiosurgery

Title

Health-related quality of life for palliative cancer care patients

Description

European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire module and Quality of Life questionnaire for palliation

Time Frame

1-, 2-, 4-, 6-, 9-, and 12-month after Stereotactic Spine Radiosurgery

Title

Local control rate at the treated index site(s)

Time Frame

From date of enrolment until the date of first documented local progression or date of death from any cause, whichever came first, assessed up to 60 months

Title

Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)

Time Frame

Within 90 days after Stereotactic Spine Radiosurgery

Title

Late toxicity (Common Toxicity Criteria for Adverse Events version 4)

Time Frame

From 90 days after Stereotactic Spine Radiosurgery until the date of death from any cause, up to 60 months

Title

Changes of spinal cord function by Frankel's classification grading system for spine injury at 4 months

Time Frame

16 weeks after Stereotactic Spine Radiosurgery

Title

Tumor-related spinal instability by the Spinal Instability Neoplastic Score (SINS) at 4 months.

Time Frame

16 weeks after Stereotactic Spine Radiosurgery

Title

Osseous changes of the treated index site(s) on CT scan within 12 months

Time Frame

2-, 4-, 6-, 9-, and 12-month after Stereotactic Spine Radiosurgery

Other Pre-specified Outcome Measures:

Title

Genomic risk of radiation induced vertebral compression fracture

Description

Assessed by grading based on vertebral height loss

Time Frame

At baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria To be eligible for inclusion, patients must fulfill the following criteria: Patients with a histologic diagnosis of non-hematopoietic malignancy Radiographic evidence of localized spine metastases without leptomeningeal involvement or intramedullary lesion Maximum three separate sites with a maximal involvement of two continuous vertebral levels Patients do not have prior radiotherapy to the index spine(s) Patients with metastatic epidural spinal cord compression (≥ grade 2) at the index spine(s) who will not be treated with spine surgery after evaluation by neurosurgeon or orthopedic doctor Age ≥ 20 years Karnofsky performance status (KPS) ≥ 60%. Life expectancy of ≥ 4 month. Women of childbearing potential and male participants must practice adequate contraception Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent Exclusion criteria Patients fulfill any of the following criteria will be excluded from this trial Prior radiotherapy to the index spine(s) Serum creatinine > 2.0 mg/dL within 90 days prior registration Contraindication to MRI such as implanted metal devices or foreign bodies, severe claustrophobia Patients with leptomeningeal involvement or intramedullary metastasis Inability to tolerate treatment procedure Bony retropulsion causing neurologic abnormality Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows: Uncontrolled active infection requiring intravenous antibiotics at the time of registration Transmural myocardial infarction ≤ 6 months prior to registration Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration Life-threatening uncontrolled clinically significant cardiac arrhythmias Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Uncontrolled psychiatric disorder Will receive any other investigational agent or chemotherapy and/or target therapies during treatment Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Feng-Ming Hsu, MD

Organizational Affiliation

National Taiwan University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Taiwan University Hospital

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

12. IPD Sharing Statement

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Single Versus Multiple Fractionated SSRS for Spinal Metastases

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