Stereotactic Radiosurgery in Metastatic Spinal Cord Compression

NCT02167633 | Terminated DMC

• 2 other identifiers: H-3-2014-050RH SRS in MESCC 2014
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To determine whether stereotactic radiosurgery of metastatic spinal cord compression is equivalent to decompressive surgery followed by external body radiation therapy to maintain ability to walk at 6 weeks.

Conditions

Spinal Cord Compression; Neoplasm Metastasis

Keywords

Radiosurgery; Laminectomy; Radiotherapy; Spinal Cord Compression; Neoplasm Metastasis; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Ability to walk

  Ability to walk determined by EQ-5D-5L

  6 weeks

Secondary Outcomes (5)

• Self reported pain

  0, 6, 12, 26, 52 weeks

• Self reported bladder control

  0, 6, 12, 26, 52 weeks

• Quality of life

  0, 6, 12, 26, 52

• Response rate

  6 weeks

• Toxicity and interventional related complications

  0, 6, 12, 26, 52 weeks

Other Outcomes (1)

• Days of treatment

  52 weeks

Study Arms (2)

Decompression surgery plus fractionated radiotherapy

ACTIVE COMPARATOR

Procedure: Decompression surgery; Radiation: Fractionated Radiotherapy; Drug: Glucocorticoids; Drug: Pantoprazole

Radiosurgery

EXPERIMENTAL

Patients treated with radiosurgery/SBRT will receive a prescribed dose of 16 Gy in one fraction to cover as large a fraction as possible the defined target volume

Radiation: Radiosurgery; Drug: Glucocorticoids; Drug: Pantoprazole

Interventions

Decompression surgery PROCEDURE

Patients will undergo posterior decompression/laminectomy on relevant spinal levels depending on neurological symptoms. If there is a need of spinal stabilization after decompression, patients will undergo posterior instrumentation with pedicle screws and titanium rods. Instrumentation will be done two or three levels above and below each level with metastatic affection.

Also known as: laminectomy

Decompression surgery plus fractionated radiotherapy

Radiosurgery RADIATION

Patients treated with radiosurgery/SBRT will receive a prescribed dose of 16 Gy in 1 fraction to cover as large a fraction as possible the defined target volume

Also known as: Stereotactic Body Radiotherapy

Radiosurgery

Fractionated Radiotherapy RADIATION

Patients allocated to surgery will receive postoperative radiotherapy commencing between 10 to 21 days after decompressive surgery. Target should include the entire vertebral body and the vertebral arch at the operated level of the vertebral column. Patients receiving postoperative radiotherapy will receive 30 Gy in 10 fractions with 3 Gy pr. fraction. The prescribed dose should cover at least 90 % of the defined target volume.

Decompression surgery plus fractionated radiotherapy

Glucocorticoids DRUG

All patients referred with clinical suspicion of metastatic spinal cord compression will receive high dose glucocorticoids. Dose adjusted to risc of side effects.

Also known as: steroids

Decompression surgery plus fractionated radiotherapy; Radiosurgery

Pantoprazole DRUG

All patients receiving high dose glucocorticoids will also be prescribed with pantoprazole 40/daily to prevent gastric ulcers

Also known as: Proton pump inhibitor (PPI)

Decompression surgery plus fractionated radiotherapy; Radiosurgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histological or cytological confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
• Patients must have localized spine metastasis from first cervical to last lumbar vertebra with evidence of radiological SCC (rSCC) on a diagnostic MRI defined as involvement or compression of either the spinal cord or the cauda equina by an epidural mass lesion or metastatic disease causing impingement, indentation or loss of definition of the thecal sac
• A maximum of two separate sites requiring treatment is allowed with maximum two vertebra pr. site
• Eligible for surgery defined by technical assessment by surgeon whether surgical decompression is possible with proper stabilization of the spine
• No medical co-morbidity contradicting anesthesia
• Patient without former treatment for metastatic spinal cord compression with either decompressive surgery and/or radiation therapy
• Patient with mild to moderate neurologic signs are eligible. These neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 on MRC scale
• Age ≥18 years
• ECOG performance status ≤2
• Life expectancy of greater than 3 months
• The effects of ionizing radiation on the developing human fetus are known to be teratogenic. For this reason women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of radiation therapy administration
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Histology of myeloma or lymphoma
• Patients with any spine metastasis that is not planned to be treated per protocol
• Spine instability due to a compression fracture or impending vertebral compression fracture
• Patients with rapid neurologic decline within 24 hours
• Bony retropulsion causing neurologic abnormality
• Prior radiation to the index spine
• Patients for whom an MRI of the spine is medically contraindicated
• Patients allergic to contrast dye used in MRIs
• Patients who are receiving any other investigational agents
• Patients with more than two known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patient with any serious neurologic condition other than MSCC that could confound the diagnosis and interpretation of radiation induced myelopathy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (17)

• Morgen SS, Lund-Andersen C, Larsen CF, Engelholm SA, Dahl B. Prognosis in patients with symptomatic metastatic spinal cord compression: survival in different cancer diagnosis in a cohort of 2321 patients. Spine (Phila Pa 1976). 2013 Jul 15;38(16):1362-7. doi: 10.1097/BRS.0b013e318294835b.

  PMID: 23574811 BACKGROUND

• Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005 Aug 20-26;366(9486):643-8. doi: 10.1016/S0140-6736(05)66954-1.

  PMID: 16112300 BACKGROUND

• Rades D, Huttenlocher S, Dunst J, Bajrovic A, Karstens JH, Rudat V, Schild SE. Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin Oncol. 2010 Aug 1;28(22):3597-604. doi: 10.1200/JCO.2010.28.5635. Epub 2010 Jul 6.

  PMID: 20606090 BACKGROUND

• George R, Jeba J, Ramkumar G, Chacko AG, Leng M, Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006716. doi: 10.1002/14651858.CD006716.pub2.

  PMID: 18843728 BACKGROUND

• Rock JP, Ryu S, Yin FF, Schreiber F, Abdulhak M. The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors. J Neurooncol. 2004 Aug-Sep;69(1-3):319-34. doi: 10.1023/b:neon.0000041890.01837.53.

  PMID: 15527098 BACKGROUND

• Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976). 2007 Jan 15;32(2):193-9. doi: 10.1097/01.brs.0000251863.76595.a2.

  PMID: 17224814 BACKGROUND

• Ryu S, Rock J, Jain R, Lu M, Anderson J, Jin JY, Rosenblum M, Movsas B, Kim JH. Radiosurgical decompression of metastatic epidural compression. Cancer. 2010 May 1;116(9):2250-7. doi: 10.1002/cncr.24993.

  PMID: 20209611 BACKGROUND

• Jin R, Rock J, Jin JY, Janakiraman N, Kim JH, Movsas B, Ryu S. Single fraction spine radiosurgery for myeloma epidural spinal cord compression. J Exp Ther Oncol. 2009;8(1):35-41.

  PMID: 19827269 BACKGROUND

• Sahgal A, Ma L, Gibbs I, Gerszten PC, Ryu S, Soltys S, Weinberg V, Wong S, Chang E, Fowler J, Larson DA. Spinal cord tolerance for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):548-53. doi: 10.1016/j.ijrobp.2009.05.023. Epub 2009 Sep 16.

  PMID: 19765914 BACKGROUND

• Kirkpatrick JP, van der Kogel AJ, Schultheiss TE. Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S42-9. doi: 10.1016/j.ijrobp.2009.04.095.

  PMID: 20171517 BACKGROUND

• Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008 Oct;18(4):215-22. doi: 10.1016/j.semradonc.2008.04.001. No abstract available.

  PMID: 18725106 BACKGROUND

• Boehling NS, Grosshans DR, Allen PK, McAleer MF, Burton AW, Azeem S, Rhines LD, Chang EL. Vertebral compression fracture risk after stereotactic body radiotherapy for spinal metastases. J Neurosurg Spine. 2012 Apr;16(4):379-86. doi: 10.3171/2011.11.SPINE116. Epub 2012 Jan 6.

  PMID: 22225488 BACKGROUND

• Cunha MV, Al-Omair A, Atenafu EG, Masucci GL, Letourneau D, Korol R, Yu E, Howard P, Lochray F, da Costa LB, Fehlings MG, Sahgal A. Vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT): analysis of predictive factors. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):e343-9. doi: 10.1016/j.ijrobp.2012.04.034. Epub 2012 Jun 1.

  PMID: 22658511 BACKGROUND

• Choi D, Morris S, Crockard A, Albert T, Bunger C, Fehlings M, Harrop J, Kawahara N, Martin JA, Massicotte EM, Mazel C, Oner FC, Peul W, Tomita K, Wang M. Assessment of quality of life after surgery for spinal metastases: position statement of the Global Spine Tumour Study Group. World Neurosurg. 2013 Dec;80(6):e175-9. doi: 10.1016/j.wneu.2013.02.054. Epub 2013 Feb 16.

  PMID: 23422266 BACKGROUND

• Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, Sheehan J, Gerszten PC, Chang E, Gibbs I, Soltys S, Sahgal A, Deasy J, Flickinger J, Quader M, Mindea S, Yamada Y. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e597-605. doi: 10.1016/j.ijrobp.2012.03.009. Epub 2012 May 19.

  PMID: 22608954 BACKGROUND

• Tokuhashi Y, Matsuzaki H, Oda H, Oshima M, Ryu J. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine (Phila Pa 1976). 2005 Oct 1;30(19):2186-91. doi: 10.1097/01.brs.0000180401.06919.a5.

  PMID: 16205345 BACKGROUND

• Suppli MH, Munck Af Rosenschold P, Dahl B, Berthelsen AK, Engelholm SA, Pappot H. Premature Termination of a Randomized Controlled Trial on Image-Guided Stereotactic Body Radiotherapy of Metastatic Spinal Cord Compression. Oncologist. 2020 Mar;25(3):210-e422. doi: 10.1634/theoncologist.2019-0672. Epub 2019 Oct 11.

  PMID: 32162821 DERIVED

MeSH Terms

Conditions

Spinal Cord Compression; Neoplasm Metastasis

Interventions

Laminectomy; Radiosurgery; Glucocorticoids; Steroids; Pantoprazole; Proton Pump Inhibitors

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Injuries; Wounds and Injuries; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Orthopedic Procedures; Therapeutics; Decompression, Surgical; Surgical Procedures, Operative; Neurosurgical Procedures; Radiotherapy; Stereotaxic Techniques; Investigative Techniques; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Fused-Ring Compounds; Polycyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Study Officials

• Morten H Suppli, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Svend Aage Engelholm, MD

  Rigshospitalet, Denmark

  STUDY DIRECTOR

• Benny Dahl, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

• Helle Pappot, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

• Per Munck af Rosenschöld, Medical Physicist

  Rigshospitalet, Denmark

  STUDY CHAIR

• Søren S Morgen, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

• Ivan Vogelius, Medicial Physicist

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 19, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: March 11, 2021

Record last verified: 2021-03

Locations

DK (1)