Esophagus-sparing Radiotherapy for Metastatic Spinal Cord Compression. (ESO-SPARE)

ESO-SPARE: Esophagus Sparring Radiotherapy for Thoracic and Cervical Metastatic Spinal Cord Compression. A Randomized Phase III Study.

Metastatic spinal cord compression (MSCC) is a serious complication to metastatic cancer and when diagnosed life expectancy is short. Treatment is palliative radiotherapy (RT). Early esophageal toxicity is underreported but can seriously impact quality of life (QoL).

The aim of the ESO-SPARE trial is to investigate if esophagus sparing RT can decrease patient reported esophageal toxicity without compromising ambulatory function or increase other toxicities.

200 patients with MSCC in the thoracic or cervical spine referred for RT will be randomized to either standard or esophagus/pharynx sparing RT. Subsequently participants will be followed with PROM (Patient Reported Outcome Measures) for 9 weeks. PROM-CTCAE questionnaires on upper GI toxicity and pain will be collected daily for 5 weeks and weekly for 4 weeks. Questionnaires evaluating QoL and physical function will be collected weekly for 9 weeks.

Study Overview

• Status: Recruiting
• Conditions: Esophagitis; Radiation Toxicity; Patient Reported Outcome Measures; Metastatic Spinal Cord Compression
• Intervention / Treatment: Radiation: Esophagus sparring radiotherapy treatment

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna M Nielsen, MD; Phone Number: 00 45 26718136; Email: anna.mann.nielsen@regionh.dk
• Study Contact Backup: Name: Gitte Persson, MD, Ph.d.; Phone Number: 00 45 38689299; Email: Gitte.Persson@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Morten H Suppli, MD, PhD.; Phone Number: 00 45 35459698; Email: morten.hiul.suppli@regionh.dk
    • Contact: Ivan R Vogelius, Dr. med, clinical proffesor; Phone Number: 00 45 35459885; Email: ivan.richter.vogelius@regionh.dk
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev Hospatal
    • Contact: Anna M Nielsen; Phone Number: +4526718136; Email: anna.mann.nielsen@regionh.dk
    • Contact: Gitte Persson; Phone Number: +4538689299; Email: Gitte.Persson@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histology or cytology proven cancer

• Referred for palliative radiotherapy of the cervical or thoracic vertebra for

  • epidural ingrowth
  • metastatic spinal cord compression
  • metastatic spinal nerve root compression
  • post-operative radiotherapy after decompressive surgery for spinal cord or nerve root compression
• Ability to understand and the willingness to sign a written informed consent document
• Referred for the following dose prescriptions 5 Gy x 5, 5 Gy x 4, 3 Gy x 10, 10 Gy x 1, 8 Gy x 1.
• ≥ 18 years old.

Exclusion Criteria:

- Referred for > 10 fractions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Arm A: standard radiotherapy treatment; Patients in arm A will receive standard radiotherapy treatment for metastatic spinal cord compression.
Experimental: Arm B: esophagus sparring radiotherapy treatment; Patients in arm B will receive esophagus sparring radiotherapy treatment.	Radiation: Esophagus sparring radiotherapy treatment; A radiotherapy plan for metastatic spinal cord compression is conducted with specific constrains sparring the esophagus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early patient reported gastro-oesophageal toxicity	Measured as a peak score using CTCAE Patient Reported Outcome Measures	Measured within the first 5 weeks after treatment start
Ambulatory function	Preserved ability to walk will be evaluated using the European Quality of Life - 5 Dimensions questionnaire (EQ-5D-5L) mobility dimension. The EQ-5D includes one question for each of the five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5).	Measured 9 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of gastro-oesophageal toxicity	Measured as the time from an increase in gastro-oesophageal symptom score to a return to baseline	Assessed 9 weeks after treatment start
Reirradiation rate - Overall survival (OS)	Defined as fraction of patients getting reirradiation, where the same spine levels are included in the irradiated volume	Assessed 6 months after inclusion of the last patient.
Patient reported physical function	Patient reported physical function will be assessed using answers from the EORTC QLQ-C30 questionnaire. Questions regarding physical function are measured on a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much). All EORTC QLQ-C30 answers will be scored according to the EORTC QLQ-C30 Scoring Manual.	Assessed Weekly over a period of 9 weeks
Health related Quality of life (QoL)	Health related quality of life measured with EQ-5D-5L European Quality of Life - 5 Dimensions questionnaire (EQ-5D-5L). The EQ-5D includes one question for each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). Health state scores are defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health). A visual analogue scale indicating the respondent's own assessment of their health status from 0-100 is also included (100 = the best health you can imagine and 0 = the worst health you can imagine).	Assessed Weekly over a period of 9 weeks
Health related Quality of life (QoL)	Health related quality of life assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire - Cancer (QLQ-C30). The EORTC QLQ-C30 consists of 30 questions assessing quality of life issues using a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much) except from the last two questions which are measured between 1 (Very Poor) to 7 (Excellent). The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual.	Assessed Weekly over a period of 9 weeks
Weight	Assessed Weekly over a period of 9 weeks	Assessed Weekly over a period of 9 weeks
Analgesic consumption	Assessed Weekly over a period of 9 weeks	Assessed Weekly over a period of 9 weeks
Pain (MSCC site)	Evaluated by "Numeric Pain Rating Scale (NPRS)" The scale is composed of 0 (no pain at all) to 10 (worst imaginable pain).	Assessed daily for 5 weeks and subsequently weekly for 4 weeks.
Pain assessment (MTS site)	Assessment will be performed using International Consensus Pain Response Endpoints (ICPRE).; A complete pain response is defined as a pain score of 0 out of 10 at the treated site with no concomitant increase in analgesic intake; A partial pain response is defined as a pain reduction of 2 or more at the treated site without analgesic increase, or an analgesic reduction of 25% with no increase in pain score or 1 point above baseline.; Pain progression is defined as an increase in pain score of 2 or more above baseline with stable analgesic intake or an analgesic increase of 25% with stable pain score.; An indeterminate response is any response not captured in the above definitions. Analysis of pain reduction will only include patients with NPRS ≥ 1 registered at baseline. We intend to report the best response during follow-up.	Best response during 9 weeks of follow-up

Collaborators and Investigators

• Sponsor: Herlev Hospital
• Collaborators: Rigshospitalet, Denmark; University of Copenhagen; Danish Cancer Society

Publications and helpful links

General Publications

• Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001 Jul;33(5):337-43. doi: 10.3109/07853890109002087.
• Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Esophagitis; Palliative radiotherapy; Patient reported outcome measures; Metastatic Spinal Cord Compression; Radiation Toxicity
• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Gastrointestinal Diseases; Gastroenteritis; Spinal Cord Diseases; Esophageal Diseases; Spinal Cord Injuries; Esophagitis; Spinal Cord Compression
• Other Study ID Numbers: AA 2112 ESO-SPARE; H-20069184 (Registry Identifier: Regional Committee on Health Research Ethics, Capital Region, Denmark)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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