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Trial record 3 of 30 for:    spinal cord injury | radiation

High-precision Radiotherapy of Motor Deficits Due to Metastatic Spinal Cord Compression (PRE-MODE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070431
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : March 3, 2020
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Prof. Dirk Rades, MD, University Hospital Schleswig-Holstein

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Spinal Cord Compression Due to Metastasis to Spine
Intervention Radiation: High-precision RT 5x5 Gy in 1 week
Enrollment 44
Recruitment Details  
Pre-assignment Details  
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Period Title: Overall Study
Started 44
Completed 40
Not Completed 4
Reason Not Completed
Withdrawal by Subject             2
Lost to Follow-up             2
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Baseline Participants 44
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age Number Analyzed 44 participants
<=65 years
30
  68.2%
>=66 years
14
  31.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
Female
16
  36.4%
Male
28
  63.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
caucasian
44
 100.0%
other
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
Germany
20
  45.5%
Spain
12
  27.3%
Slovenia
9
  20.5%
Georgia
3
   6.8%
primary tumor type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
breast cancer
9
  20.5%
prostate cancer
3
   6.8%
myeloma/lymphoma
5
  11.4%
lung cancer
13
  29.5%
other tumors
14
  31.8%
interval from tumor diagnosis to MSCC  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
<=15 months
23
  52.3%
>15 months
21
  47.7%
number of involved vertebrae  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
1-2
30
  68.2%
>=3
14
  31.8%
other bone metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
no
10
  22.7%
yes
34
  77.3%
visceral metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
no
16
  36.4%
yes
28
  63.6%
time developing motor deficits  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
1-7 days
14
  31.8%
8-14 days
10
  22.7%
>14 days
20
  45.5%
ambulatory status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
not ambulatory
18
  40.9%
ambulatory
26
  59.1%
Eastern Cooperative Oncology Group performance score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
ECOG 1-2
20
  45.5%
ECOG 3-4
24
  54.5%
[1]
Measure Description:

Performance status was rated with the Eastern Cooperative Oncology Group (ECOG), ranging from 0 to 5 (lower grade=better performance status).

0: Fully active without restrictions.

  1. Restricted in physically strenuous activity; ambulatory and able to perform light or sedentary work.
  2. Ambulatory and capable of all self-care; unable to work; up and about >50% of hours awake.
  3. Capable of limited self-care; confined to bed/chair >50% of hours awake.
  4. Completely disabled. Totally confined to bed or chair.
  5. Dead.

[Oken et al., Am J Clin Oncol 1982;5:649-55.]

motor function  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
ambulatory without aid
15
  34.1%
ambulatory with aid
12
  27.3%
not ambulatory
15
  34.1%
complete paraplegia
2
   4.5%
sensory function  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
absent
0
   0.0%
impaired
17
  38.6%
normal
23
  52.3%
unclear
4
   9.1%
sphincter dysfunction  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
no
37
  84.1%
yes
6
  13.6%
unclear
1
   2.3%
Distress (measured with the distress-thermometer)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
0-1 points
1
   2.3%
2-4 points
11
  25.0%
5-7 points
15
  34.1%
8-10 points
16
  36.4%
not available
1
   2.3%
[1]
Measure Description:

Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. The patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.

[Holland JC, et al. J Natl Comp Cancer Network 2013;11:190-209.]

Pain (measured with a numeric self-rating scale)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
0-1 points
8
  18.2%
2-4 points
11
  25.0%
5-7 points
14
  31.8%
8-10 points
11
  25.0%
[1]
Measure Description: Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).
1.Primary Outcome
Title Number of Participants Who Were Alive at 6 Months After Radiotherapy Without Deterioration of Motor Function During (or Directly After) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy
Hide Description

Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.

An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.

In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.

Time Frame 6 months after the end of radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision Radiotherapy 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision radiotherapy 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.0
(81.5 to 98.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-precision Radiotherapy 5x5 Gy in 1 Week
Comments historical control group treated with 5 x 4 Gy
Type of Statistical Test Superiority
Comments It was assumed that radiotherapy with 5x4 Gy results in 6-month LPFS of 67% and an increase by 20% is clinically relevant when using 5x5 Gy. For comparison of 5x5 Gy and a historical control (5x4 Gy), it was assumed that it can be performed with a simple Pearson-Chi-Square test (2-sided significance level of 5%, power of 79%) if 40 patients treated with 5x5 Gy and 400 patients of the control group qualified for Propensity-Score adjusted comparison, assuming 6-month LPFS rates of 87% and 67%.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 20
Estimation Comments [Not Specified]
Other Statistical Analysis

In a prospective study, 6-month LPFS rates were 86% after longer-course (mainly 3Gyx10) and 67% after short-course radiotherapy (mainly 4Gyx5) [Rades D, et al., Int J Radiat Oncol Biol Phys 2009;73:228-34.]. For sample size calculations, it was assumed that conventional radiotherapy with 4Gyx5 results in 6-month LPFS of 67% and that an increase by 20% is clinically relevant and realistic with 5Gyx5. A sample size of 40 eligible patients was required for the phase 2 trial assuming that that 6-month LPFS would be 87% and estimated with a precision of +/-20% expressed as the half length of the associated two-sided confidence interval (95%), and power of >=80%.

For comparison of phase 2 cohort and historical control group, it was assumed that this could be performed with a simple Pearson-Chi-Square test using a two-sided significance level of 5% (10%) and a power of 79% (86%) if 40 patients received 5Gyx5 and N=400 of the control group qualified for Propensity-Score adjusted comparison.

2.Secondary Outcome
Title Number of Participants Showing Improvement of Motor Deficits Following Radiotherapy (Best Response)
Hide Description

Motor function was evaluated using the following scale. Improvement of motor function was defined as a decrease of at least 1 point.

0 = Normal strength

  1. = Ambulatory without aid
  2. = Ambulatory with aid
  3. = Not ambulatory
  4. = Complete paraplegia

[Tomita T, et al., Acta Radiol Oncol 1983;22:135-143.]

Time Frame up to 6 months following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
improvement of motor function
24
  60.0%
no improvement of motor deficits
16
  40.0%
3.Secondary Outcome
Title Number of Participants Showing Improvement of Sensory Function Following Radiotherapy (Best Response)
Hide Description

Sensory function was evaluated with the following scale, modified in accordance to the classification of the American Spinal Injury Association.

0 = Absent

  1. = Impaired
  2. = Normal

9 = Cannot be assessed

[Baskin DS. Spinal cord injury. In Evans RW (Ed.), Neurology and trauma, WB Saunders, Philadelphia;1996, pp. 276-299.]

Time Frame up to 6 months following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had sensory deficits prior to the start of radiotherapy.
Arm/Group Title Patients With Sensory Deficits at Baseline
Hide Arm/Group Description:
Patients who had sensory deficits prior to the start of radiotherapy.
Overall Number of Participants Analyzed 16
Measure Type: Count of Participants
Unit of Measure: Participants
improvement of sensory deficits
8
  50.0%
no improvement of sensory deficits
8
  50.0%
4.Secondary Outcome
Title Number of Participants Showing Improvement of Sphincter Dysfunction Following Radiotherapy (Best Response)
Hide Description Sphincter dysfunction was rates as yes (presence of sphincter dysfunction) or no (absence of sphincter dysfunction).
Time Frame up to 6 months following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had a sphincter dysfunction prior to the start of radiotherapy.
Arm/Group Title Patients With Sphincter Dysfunction at Baseline
Hide Arm/Group Description:
Patients who had a sphincter dysfunction prior to the start of radiotherapy.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
improvement
2
  33.3%
no improvement
2
  33.3%
post-treatment assessment not available
2
  33.3%
5.Secondary Outcome
Title Number of Participants Who Were Alive at 3 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy
Hide Description

Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.

An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.

In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy. The values of 3-month LPFS were estimated using the Kaplan-Meier method.

Time Frame 3 months after the end of radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95
(82 to 99)
6.Secondary Outcome
Title Number of Participants Who Were Alive at 6 Months Following Radiotherapy
Hide Description Overall Survival (OS) was defined as freedom from death of any cause. Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.
Time Frame 6 months after the end of radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45.0
(26.7 to 57.6)
7.Secondary Outcome
Title Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline
Hide Description

Vertebral pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).

Pain relief was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.

Time Frame Evaluation at 1 month following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patients With a Pain Score of >1 at Baseline
Hide Arm/Group Description:
Patients who had a pain score of >1 prior to the start of RT and were evaluable for pain relief at 1 month following RT.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
pain relief
13
  61.9%
no pain relief
8
  38.1%
8.Secondary Outcome
Title Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline
Hide Description

Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.

An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.

Time Frame Evaluation at 1 month following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patients With a Distress Score of >1 at Baseline
Hide Arm/Group Description:
Patients who had a distress score of >1 prior to the start of RT and were evaluable for relief of distress at 1 month following RT.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
relief of distress
13
  54.2%
no relief of distress
11
  45.8%
9.Secondary Outcome
Title Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity
Hide Description Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)
Time Frame during radiotherapy and up to 6 months following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
grade 2-3 toxicity toxicity
4
  10.0%
no toxicity
36
  90.0%
grade 3 toxicity toxicity
1
   2.5%
no toxicity
39
  97.5%
10.Secondary Outcome
Title Number of Participants Who Were Able to Walk Following Radiotherapy
Hide Description

Ambulatory status was assessed using the following scoring system:

0=Normal strength

  1. Ambulatory without aid
  2. Ambulatory with aid
  3. Not ambulatory

A patient with a score equal to or less than 2 is considered "able to walk". Both participants that could and could not walk prior to radiotherapy have been included in this assessment.

Time Frame up to 6 months following radiotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description:

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
able to walk following radiotherapy
33
  82.5%
not able to walk following radiotherapy
7
  17.5%
Time Frame during the period of radiotherapy and up to 6 months during the period of follow up
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title High-precision RT 5x5 Gy in 1 Week
Hide Arm/Group Description

Patients with motor deficits of the lower extremities due to metastatic spinal cord compression (MSCC) will receive 5x5 Gy of high-precision RT in 1 week.

High-precision RT 5x5 Gy in 1 week: Patients included in this study will receive a high-precision radiotherapy with 5x5 Gy in 1 week

All-Cause Mortality
High-precision RT 5x5 Gy in 1 Week
Affected / at Risk (%)
Total   22/40 (55.00%)    
Hide Serious Adverse Events
High-precision RT 5x5 Gy in 1 Week
Affected / at Risk (%) # Events
Total   5/40 (12.50%)    
Cardiac disorders   
Heart failiure * 1  1/40 (2.50%)  1
Infections and infestations   
Systemic aspergillosis * 1  1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonia * 1  1/40 (2.50%)  1
Unknown death (shortness of breath) * 1  1/40 (2.50%)  1
Vascular disorders   
Pulmonary embolism * 1  1/40 (2.50%)  1
1
Term from vocabulary, CTCAE v4.03
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
High-precision RT 5x5 Gy in 1 Week
Affected / at Risk (%) # Events
Total   10/40 (25.00%)    
Gastrointestinal disorders   
Nausea * 1  10/40 (25.00%)  17
Diarrhea * 1  7/40 (17.50%)  13
General disorders   
Fatigue * 1  2/40 (5.00%)  3
1
Term from vocabulary, CTCAE 4.03 (MedDRA)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Dr. med. Dirk Rades
Organization: Department of Radiation Oncology, University of Lübeck, Lübeck, Germany
Phone: 0049 451 500 ext 45400
EMail: rades.dirk@gmx.net
Layout table for additonal information
Responsible Party: Prof. Dirk Rades, MD, University Hospital Schleswig-Holstein
ClinicalTrials.gov Identifier: NCT03070431    
Other Study ID Numbers: PRE-MODE
First Submitted: February 27, 2017
First Posted: March 3, 2017
Results First Submitted: January 30, 2020
Results First Posted: March 3, 2020
Last Update Posted: March 3, 2020