RAdiotherapy for Metastatic Spinal Cord Compression With Increased Radiation dosES (RAMSES-01)

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.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Compression Due to Metastasis to Spine
• Intervention / Treatment: Radiation: High-precision RT

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.

• Study Type: Interventional
• Enrollment (Anticipated): 65
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dirk Rades, Prof. Dr.; Phone Number: 45401 +49-451-500; Email: dirk.rades@uksh.de
• Study Contact Backup: Name: Liesa Dziggel, Dr. med.; Phone Number: 45401 +49-451-500; Email: liesa.dziggel@uksh.de

Study Locations

• Germany
  • Lubeck Hansestadt, Germany, 23562
    • Recruiting
    • Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23562 Lübeck, Germany
    • Contact: Liesa Dziggel, Dr. med.; Phone Number: +49-451-500-45410; Email: liesa.dziggel@uksh.de
    • Sub-Investigator: Christian Staackmann

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:

1. Motor deficits of the lower extremities resulting from MSCC, which have persisted for no longer than 30 days
2. Confirmation of diagnosis by MR-imaging (computed tomography [CT] allowed)
3. Age 18 years or older
4. Written informed consent
5. Favorable survival prognosis (defined as 36-45 points on the survival score)
6. Capacity of the patient to contract

Exclusion Criteria:

1. Previous RT or surgery of the spinal areas affected by MSCC
2. Symptomatic brain tumor or symptomatic brain metastases
3. Metastases of the cervical spine only
4. Other severe neurological disorders
5. Pregnancy, Lactation
6. Clear indication for spinal surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High-precision RT; Study Arm: 18 x 2.33 Gy of high-precision RT in 3.5 weeks.	Radiation: High-precision RT; 18 x 2.33 Gy of high-precision RT in 3.5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	For each patient 12 months after the end of RT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessment directly and at 1, 3, 6, 9 and 12 months after RT.
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	Evaluation directly and at 1, 3, 6, 9 and 12 months after 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.	Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
Overall survival	Will be calculated from the last day of RT up to 12 months following RT.	Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
Local progression-free survival	LPFS time will be calculated from the last day of the RT.	Additional evaluation directly and 1, 3, 6 and 9 months after 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.	Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after 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.	Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
Chance in sphincter dysfunction	Sphincter dysfunction will be evaluated as yes versus no.	Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Investigators: Principal Investigator: Dirk Rades, Prof. Dr., Dep. of Radiation Oncology, Univ. of Lübeck and Univ. Medical Center S-H

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 8, 2019
• Primary Completion (ANTICIPATED): August 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (ACTUAL): August 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: spinal cord compression, radiotherapy
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Spinal Cord Diseases; Spinal Cord Injuries; Spinal Cord Compression
• Other Study ID Numbers: RAMSES-01

Drug and device information, study documents

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