Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression

Metastatic Epidural Spinal Cord Compression Clinical Trial

— SCORE-2  

Official title:

Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression (10 x 3 Gy Versus 5 x 4 Gy)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02189473
• Other study ID #: ARO 200901
• Status: Completed
• Phase: N/A
• Start date: July 2010
• Est. completion date: July 2015

Study information

• Verified date: February 2020
• Source: University of Schleswig-Holstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary aim of this randomized multi-center trial is to investigate the efficacy of the radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in patients with metastatic epidural spinal cord compression.

Description:

The primary aim of this randomized multi-center trial is to investigate the efficacy of the radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in patients with metastatic epidural spinal cord compression. The response rate (improvement in motor function or prevention of progression) will be assessed at one month following radiotherapy.

In addition, the following endpoints will be evaluated:

1. Motor function; additional assessments directly and at 3 and at 6 months after radiotherapy

2. Ability to walk; assessment directly and at 1, 3 and 6 months after radiotherapy

3. Sensory function; assessment directly and at 1, 3 and 6 months after radiotherapy

4. Quality of life; evaluation directly and at 1, 3 and 6 months after radiotherapy

5. Pain assessment directly and at 1, 3 and 6 months after radiotherapy

6. Overall survival up to 6 months following radiotherapy

7. Local Progression-free survival up to 6 months following radiotherapy

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Motor deficits of the lower extremities resulting from metastatic epidural spinal cord compression, which have persisted for no longer than 30 days

• Confirmation of diagnosis by magnetic resonance imaging (spinal computed tomography allowed)

• Relatively poor survival prognosis (defined as =35 points on the survival score published in Cancer 2008)

• Written informed consent

Exclusion Criteria:

• Prior radiotherapy or surgery of the spinal areas affected by MESCC

• History of symptomatic brain tumor or symptomatic brain metastases

• Metastases of the cervical spine only

• Other severe neurological disorders

• Pregnancy, Lactation

• Indication for decompressive surgery + stabilization of the affected spinal areas

Related Conditions & MeSH terms

• Metastatic Epidural Spinal Cord Compression
• Spinal Cord Compression

Intervention

Radiation:
• radiotherapy
external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)

Locations

Country	Name	City	State
Germany	Klinikum Bayreuth	Bayreuth	Bavaria
Germany	Charite Berlin	Berlin
Germany	Ruhr University	Bochum	North Rhine Westphalia
Germany	Center of Radiotherapy and Radiation Oncology	Bremen
Germany	Radiotherapy Practice Dresden-Friedrichstadt	Dresden	Saxonia
Germany	University of Lübeck	Lübeck	Schleswig-Holstein
Germany	Oberschwabenklinik Ravensburg	Ravensburg	Baden-Wutemberg
Germany	University of Regensburg	Regensburg	Bavaria
Germany	University of Würzburg	Würzburg	Bavaria
Lithuania	Institute of Oncology, Vilnius University	Vilnius
Saudi Arabia	Saad Specialist Hospital	Khobar
Slovenia	Institute of Oncology	Ljubljana
Spain	Cruces University Hospital	Barakaldo	Vizcaya (Basque Country)
Spain	Consorcio Hospitalario Provencial de Castellon	Valencia	Castellon
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Prof. Dirk Rades, MD

Countries where clinical trial is conducted

United States,  Germany,  Lithuania,  Saudi Arabia,  Slovenia,  Spain, 

References & Publications (18)

8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Radiother Oncol. 1999 Aug;52(2):111-21. — View Citation

Arcangeli G, Giovinazzo G, Saracino B, D'Angelo L, Giannarelli D, Arcangeli G, Micheli A. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1119-26. — View Citation

Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1981-97. Review. — View Citation

Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. Review. — View Citation

Helweg-Larsen S, Sørensen PS, Kreiner S. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000 Mar 15;46(5):1163-9. — View Citation

Koswig S, Budach V. [Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study]. Strahlenther Onkol. 1999 Oct;175(10):500-8. German. — View Citation

Leviov M, Dale J, Stein M, Ben-Shahar M, Ben-Arush M, Milstein D, Goldsher D, Kuten A. The management of metastatic spinal cord compression: a radiotherapeutic success ceiling. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):231-4. — View Citation

Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, Mignogna M, Beneventi S, Lupattelli M, Ponticelli P, Biti GP, Latini P. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005 May 20;23(15):3358-65. Epub 2005 Feb 28. — View Citation

Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):959-67. — View Citation

Niewald M, Tkocz HJ, Abel U, Scheib T, Walter K, Nieder C, Schnabel K, Berberich W, Kubale R, Fuchs M. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1085-9. — View Citation

Rades D, Blach M, Bremer M, Wildfang I, Karstens JH, Heidenreich F. Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1403-8. — View Citation

Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer. 2008 Jan 1;112(1):157-61. — View Citation

Rades D, Heidenreich F, Bremer M, Karstens JH. Time of developing motor deficits before radiotherapy as a new and relevant prognostic factor in metastatic spinal cord compression: final results of a retrospective analysis. Eur Neurol. 2001;45(4):266-9. — View Citation

Rades D, Heidenreich F, Karstens JH. Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):975-9. — View Citation

Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005 May 20;23(15):3366-75. — View Citation

Sørensen S, Børgesen SE, Rohde K, Rasmusson B, Bach F, Bøge-Rasmussen T, Stjernholm P, Larsen BH, Agerlin N, Gjerris F, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer. 1990 Apr 1;65(7):1502-8. — View Citation

Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Wárlám-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999 Aug;52(2):101-9. Erratum in: Radiother Oncol 1999 Nov;53(2):167. Leer, J [corrected to Leer, JW]; van Mierlo ,T [corrected to van Mierlo, I]. — View Citation

Tomita T, Galicich JH, Sundaresan N. Radiation therapy for spinal epidural metastases with complete block. Acta Radiol Oncol. 1983;22(2):135-43. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy	Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.; Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.; Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).	at 1 month following radiotherapy
Secondary	Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy	Ambulatory status was assessed using the following scoring system: 0 = Normal strength; = Ambulatory without aid; = Ambulatory with aid; = 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..	at 1 month following radiotherapy
Secondary	Number of Participants Who Were Alive at 6 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	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.	6 months following radiotherapy
Secondary	Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline	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.	at 1 month following radiotherapy
Secondary	Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline	Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).; Relief of pain 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.	at 1 month following radiotherapy
Secondary	Number of Participants Who Were Alive at 6 Months Following Radiotherapy	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.	6 months following radiotherapy
Secondary	Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy	Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.; Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.	at 1 month following radiotherapy
Secondary	Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity	Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)	during radiotherapy and up to 6 months following radiotherapy