RAdiotherapy for Metastatic Spinal Cord Compression With Increased Radiation dosES (RAMSES-01)
Primary Purpose
Spinal Cord Compression Due to Metastasis to Spine
Status
Unknown status
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
High-precision RT
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Compression Due to Metastasis to Spine focused on measuring spinal cord compression, radiotherapy
Eligibility Criteria
Inclusion Criteria:
- Motor deficits of the lower extremities resulting from MSCC, which have persisted for no longer than 30 days
- Confirmation of diagnosis by MR-imaging (computed tomography [CT] allowed)
- Age 18 years or older
- Written informed consent
- Favorable survival prognosis (defined as 36-45 points on the survival score)
- Capacity of the patient to contract
Exclusion Criteria:
- Previous RT or surgery of the spinal areas affected by MSCC
- Symptomatic brain tumor or symptomatic brain metastases
- Metastases of the cervical spine only
- Other severe neurological disorders
- Pregnancy, Lactation
- Clear indication for spinal surgery
Sites / Locations
- Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23562 Lübeck, GermanyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
High-precision RT
Arm Description
Study Arm: 18 x 2.33 Gy of high-precision RT in 3.5 weeks.
Outcomes
Primary Outcome Measures
Local progression-free survival at 12 months following RT.
LPFS time will be calculated from the last day of the RT. The evaluation will be performed in those patients, who are available for assessement of the Primary endpoint and have received at least 80% of the planned RT dose.
Secondary Outcome Measures
Change in motor function/ability to walk
Change in motor function is defined as improvement or deterioration by at least one point. 0=normal strength; 1=ambulatory without aid; 2 ambulatory with aid; 3=not ambulatory;4=complete paraplegia. Motor function will additionally be evaluated using additionally the American Spinal Injury Association (ASIA) classification resulting in total points of 0 to 14.
Change in quality of life
Quality of life (QoL) will be assessed using the distress thermometer. Patients can rate their impairment in QoL between 0 and 10 (no to maximum impairment). The data will be compared to the data documented prior to RT
Change in vertebral pain
Vertebral pain will be evaluated with a numeric rating scale (self-assessment by patients ) from 0=no pain to 10=worst pain. Improvement by 2 points is rated partial response, 0 points complete response. The data will be compared to the data documented prior to RT. The intake of analgesics will be included.
Overall survival
Will be calculated from the last day of RT up to 12 months following RT.
Local progression-free survival
LPFS time will be calculated from the last day of the RT.
Occurence of toxicity
Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.3. If radiation myelopathy is suspected, spinal Magnetic Resonance (MR)-Imaging will be performed. The data will be compared to the data documented prior to RT.
Change in sensory function
Sensory function will be evaluated using the following scale, modified in accordance to the ASIA classification, 0=absent, 1=impaired, 2=normal, 9=cannot be assessed.
Chance in sphincter dysfunction
Sphincter dysfunction will be evaluated as yes versus no.
Full Information
NCT ID
NCT04043156
First Posted
July 30, 2019
Last Updated
April 28, 2021
Sponsor
University Hospital Schleswig-Holstein
1. Study Identification
Unique Protocol Identification Number
NCT04043156
Brief Title
RAdiotherapy for Metastatic Spinal Cord Compression With Increased Radiation dosES
Acronym
RAMSES-01
Official Title
RAdiotherapy for Metastatic Spinal Cord Compression With Increased Radiation dosES
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 8, 2019 (Actual)
Primary Completion Date
August 30, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Schleswig-Holstein
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This clinical study aims to investigate whether high-precision radiotherapy, as supposed, leads to a better control of the irradiated spinal cord metastases when compared to conventional radiotherapy. This means that a progression or recurrence of motor deficits (weakness) of the legs following radiotherapy can be avoided more effectively. Furthermore, the high-precision radiotherapy will be compared to the conventional radiotherapy with respect to pain relief, motor function/ability to walk, quality of life, side effects and survival.
Detailed Description
The aim of this single-arm study is to show that high-precision radiotherapy (RT) with 18x2.33 Gy in 3.5 weeks results in significantly better local progression free survival (LPFS) of metastatic spinal cord compression (MSCC) when compared to conventional RT with 10x3 Gy in 2 weeks. If such superiority could be shown, 18x2.33 Gy could be recommended, at least for those patients with favourable survival prognoses, since an in-field recurrence of MSCC in the irradiated part of the spine is generally very difficult to treat.
For this investigation the newly prospectively collected data will be compared with a historical cohort collected up to the time of data analysis.
The recruitment of all 65 patients (62 patients + 5% for potential drop-outs) is planned to be completed within 21 months. The follow-up period will be 12 months. This equals a total running time for the study of 33 months.
In accordance with a previous study assessing local control of MSCC, the following patient characteristics will be recorded to allow adequate comparison with the historical control group:
Age
Gender
Type of primary tumor (breast cancer vs. prostate cancer vs. myeloma/ lymphoma vs. lung cancer vs. other tumors)
Interval from tumor diagnosis to MSCC (≤15 months vs. >15 months)
Number of involved vertebrae (1-2 vs. ≥3)
Other bone metastases at the time of RT (no vs. yes)
Visceral metastases at the time of RT (no vs. yes)
Time developing motor deficits prior to RT (1-7 days vs. 8-14 days vs. >14 days)
Ambulatory status prior to RT (no vs. yes)
Eastern Cooperative Oncology Group (ECOG) performance score (0-2 vs- 3-4)
Indication for decompressive surgery of affected spinal areas
The patients of this study who received high-precision RT with 18x2.33 Gy for MSCC will be compared to a historical control group of patients with a favorable survival prognosis who were treated with 10x3 Gy of conventional RT. The historical control group will include data from 235 patients qualifying for the comparison with the prospectively collected data.
Data for the historical control group will be collected from an already existing anonymized database with previous study data documented in the European Union.
To be eligible for control group, patients fulfilling the same inclusion criteria and exclusion criteria as defined in the prospective study are considered. Furthermore, to be consistent with efficacy analysis of the study, patients of the historical control group must have received at least 80% of the planned RT dose.
Propensity score techniques will be applied to reduce confounding due to differences between the historical control group and the prospective trial data.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Compression Due to Metastasis to Spine
Keywords
spinal cord compression, radiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single arm study compared with a historical cohort.
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High-precision RT
Arm Type
Experimental
Arm Description
Study Arm: 18 x 2.33 Gy of high-precision RT in 3.5 weeks.
Intervention Type
Radiation
Intervention Name(s)
High-precision RT
Intervention Description
18 x 2.33 Gy of high-precision RT in 3.5 weeks
Primary Outcome Measure Information:
Title
Local progression-free survival at 12 months following RT.
Description
LPFS time will be calculated from the last day of the RT. The evaluation will be performed in those patients, who are available for assessement of the Primary endpoint and have received at least 80% of the planned RT dose.
Time Frame
For each patient 12 months after the end of RT.
Secondary Outcome Measure Information:
Title
Change in motor function/ability to walk
Description
Change in motor function is defined as improvement or deterioration by at least one point. 0=normal strength; 1=ambulatory without aid; 2 ambulatory with aid; 3=not ambulatory;4=complete paraplegia. Motor function will additionally be evaluated using additionally the American Spinal Injury Association (ASIA) classification resulting in total points of 0 to 14.
Time Frame
Assessment directly and at 1, 3, 6, 9 and 12 months after RT.
Title
Change in quality of life
Description
Quality of life (QoL) will be assessed using the distress thermometer. Patients can rate their impairment in QoL between 0 and 10 (no to maximum impairment). The data will be compared to the data documented prior to RT
Time Frame
Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
Title
Change in vertebral pain
Description
Vertebral pain will be evaluated with a numeric rating scale (self-assessment by patients ) from 0=no pain to 10=worst pain. Improvement by 2 points is rated partial response, 0 points complete response. The data will be compared to the data documented prior to RT. The intake of analgesics will be included.
Time Frame
Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
Title
Overall survival
Description
Will be calculated from the last day of RT up to 12 months following RT.
Time Frame
Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
Title
Local progression-free survival
Description
LPFS time will be calculated from the last day of the RT.
Time Frame
Additional evaluation directly and 1, 3, 6 and 9 months after RT
Title
Occurence of toxicity
Description
Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.3. If radiation myelopathy is suspected, spinal Magnetic Resonance (MR)-Imaging will be performed. The data will be compared to the data documented prior to RT.
Time Frame
Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
Title
Change in sensory function
Description
Sensory function will be evaluated using the following scale, modified in accordance to the ASIA classification, 0=absent, 1=impaired, 2=normal, 9=cannot be assessed.
Time Frame
Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
Title
Chance in sphincter dysfunction
Description
Sphincter dysfunction will be evaluated as yes versus no.
Time Frame
Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Motor deficits of the lower extremities resulting from MSCC, which have persisted for no longer than 30 days
Confirmation of diagnosis by MR-imaging (computed tomography [CT] allowed)
Age 18 years or older
Written informed consent
Favorable survival prognosis (defined as 36-45 points on the survival score)
Capacity of the patient to contract
Exclusion Criteria:
Previous RT or surgery of the spinal areas affected by MSCC
Symptomatic brain tumor or symptomatic brain metastases
Metastases of the cervical spine only
Other severe neurological disorders
Pregnancy, Lactation
Clear indication for spinal surgery
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dirk Rades, Prof. Dr.
Phone
+49-451-500
Ext
45401
Email
dirk.rades@uksh.de
First Name & Middle Initial & Last Name or Official Title & Degree
Liesa Dziggel, Dr. med.
Phone
+49-451-500
Ext
45401
Email
liesa.dziggel@uksh.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Rades, Prof. Dr.
Organizational Affiliation
Dep. of Radiation Oncology, Univ. of Lübeck and Univ. Medical Center S-H
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23562 Lübeck, Germany
City
Lubeck Hansestadt
ZIP/Postal Code
23562
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dirk Rades, Professor
Phone
+49-451-500-45400
Email
dirk.rades@uksh.de
First Name & Middle Initial & Last Name & Degree
Liesa Dziggel, Dr. med.
Phone
+49-451-500-45410
Email
liesa.dziggel@uksh.de
First Name & Middle Initial & Last Name & Degree
Christian Staackmann
12. IPD Sharing Statement
Citations:
PubMed Identifier
31783816
Citation
Rades D, Hansen O, Jensen LH, Dziggel L, Staackmann C, Doemer C, Cacicedo J, Conde-Moreno AJ, Segedin B, Ciervide-Jurio R, Rubio-Rodriguez C, Perez-Romasanta LA, Alvarez-Gracia A, Dennis K, Ferrer-Albiach C, Navarro-Martin A, Lopez-Campos F, Jankarashvili N, Janssen S, Olbrich D, Hollander NH. Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study. BMC Cancer. 2019 Nov 29;19(1):1163. doi: 10.1186/s12885-019-6390-x.
Results Reference
derived
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RAdiotherapy for Metastatic Spinal Cord Compression With Increased Radiation dosES
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