Kypho-IORT vs. EBRT in Spinal Metastases

NCT02773966 | Terminated Phase 3 DMC

• 1 other identifier: Kypho-IORT/EBRT
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this randomized phase III study is to test the superiority of Kypho-IORT compared to EBRT with regard of time to pain reduction in patients with painful vertebral metastases. Therefore patients will receive intraoperative radiotherapy (8 Gy with Intrabeam System/Carl Zeiss) during kyphoplasty (Arm A) or external beam radiotherapy with 30 Gy, added in 3 Gy per fraction on a conventional linear accelerator or 8 Gy single dose (only for international study centers, not permitted in Germany) (Arm B).

Conditions

Metastasis

Outcome Measures

Primary Outcomes (1)

• pain evaluation

  Evaluation of the percentage of patients with a pain reduction of VAS-3 points after Kypho-IORT vs. EBRT at day 1 (one day after Kypho-IORT; one day after the first EBRT)

  day 1

Secondary Outcomes (4)

• pain evaluation

  week 2, 6 weeks after start of treatment

• local recurrence rate

  6 weeks, then after 3 months, then every 6 months up to 5 years

• Quality of life (QoL) questionaire

  before start of therapy and then 6 weeks, then after 3 months, then every 6 months up to 5 years

• Overall survival

  12 Months

Study Arms (2)

Arm A: Kypho-IORT

EXPERIMENTAL

balloon kyphoplasty/vertebroplasty + intraoperative radiotherapy

Radiation: Kypho-IORT

Arm B: EBRT

ACTIVE COMPARATOR

external beam radiotherapy with 30 Gy during 10 days (3 Gy/day)

Radiation: EBRT

Interventions

Kypho-IORT RADIATION

During kyphoplasty/vertebroplasty a intraoperative radiotherapy of the affected vertebrae is done with a miniature X-ray generator (INTRABEAM®, Carl Zeiss, Surgical, Oberkochen, Germany). The prescription dose will be 8 Gy in a distance of 13 mm from the isocenter of the radiation source. IORT will take about five minutes. After radiation the applicator will be removed and the operation will be finished as usual.

Arm A: Kypho-IORT

EBRT RADIATION

The external beam radiotherapy will be usually carried out as an outpatient procedure. All patients will receive a planning CT before the first irradiation. EBRT will be performed with 30 Gy, added in 3 Gy per fraction or 8 Gy single dose (only for international study centers, not permitted in Germany) on a conventional linear accelerator (LINAC).

Arm B: EBRT

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 50 years
• Karnofsky Index ≥ 60
• Initial pain score using the VAS ≥ 3 under standard pain medication
• Histological or by imaging proven painful osteolytic metastases (max. 4 treatable vertebrae) of the thoracic/lumbar spine, which are accessible for Kypho-IORT
• Written informed consent obtained

You may not qualify if:

• Previous local treatment (irradiation, surgery)
• Cranial site of the metastasis above T4
• Pathological fracture with sintering \>50%
• Purely osteoblastic metastasis
• Intraspinal extension
• Erosion of the bony borders of the vertebra which make a cement filling difficult, rated by the treating surgeon
• Tumor expansion to dorsal vertebral structures (pedicle, lamina)
• Pregnancy/lactation

Sponsors & Collaborators

• Universitätsmedizin Mannheim: lead

Study Sites (1)

Department of Radiotherapy University Hospital Mannheim

Mannheim, 68167, Germany

Location

Related Publications (11)

• Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: what are the options, indications, and outcomes? Spine (Phila Pa 1976). 2009 Oct 15;34(22 Suppl):S78-92. doi: 10.1097/BRS.0b013e3181b8b6f5.

  PMID: 19829280 BACKGROUND

• Souchon R, Wenz F, Sedlmayer F, Budach W, Dunst J, Feyer P, Haase W, Harms W, Sautter-Bihl ML, Sauer R; German Society of Radiation Oncology (DEGRO). DEGRO practice guidelines for palliative radiotherapy of metastatic breast cancer: bone metastases and metastatic spinal cord compression (MSCC). Strahlenther Onkol. 2009 Jul;185(7):417-24. doi: 10.1007/s00066-009-2044-2. Epub 2009 Aug 28.

  PMID: 19714302 BACKGROUND

• Berenson J, Pflugmacher R, Jarzem P, Zonder J, Schechtman K, Tillman JB, Bastian L, Ashraf T, Vrionis F; Cancer Patient Fracture Evaluation (CAFE) Investigators. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):225-35. doi: 10.1016/S1470-2045(11)70008-0. Epub 2011 Feb 16.

  PMID: 21333599 BACKGROUND

• Schneider F, Greineck F, Clausen S, Mai S, Obertacke U, Reis T, Wenz F. Development of a novel method for intraoperative radiotherapy during kyphoplasty for spinal metastases (Kypho-IORT). Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1114-9. doi: 10.1016/j.ijrobp.2010.07.1985. Epub 2010 Oct 8.

  PMID: 20934272 BACKGROUND

• Wenz F, Schneider F, Neumaier C, Kraus-Tiefenbacher U, Reis T, Schmidt R, Obertacke U. Kypho-IORT--a novel approach of intraoperative radiotherapy during kyphoplasty for vertebral metastases. Radiat Oncol. 2010 Feb 11;5:11. doi: 10.1186/1748-717X-5-11.

  PMID: 20149237 BACKGROUND

• Schmidt R, Wenz F, Reis T, Janik K, Bludau F, Obertacke U. Kyphoplasty and intra-operative radiotheray, combination of kyphoplasty and intra-operative radiation for spinal metastases: technical feasibility of a novel approach. Int Orthop. 2012 Jun;36(6):1255-60. doi: 10.1007/s00264-011-1470-9. Epub 2012 Jan 22.

  PMID: 22270861 BACKGROUND

• Reis T, Schneider F, Welzel G, Schmidt R, Bludau F, Obertacke U, Wenz F. Intraoperative radiotherapy during kyphoplasty for vertebral metastases (Kypho-IORT): first clinical results. Tumori. 2012 Jul-Aug;98(4):434-40. doi: 10.1177/030089161209800406.

  PMID: 23052158 BACKGROUND

• Bludau F, Welzel G, Reis T, Schneider F, Sperk E, Neumaier C, Ehmann M, Clausen S, Obertacke U, Wenz F, Giordano FA. Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases. Spine J. 2018 May;18(5):776-781. doi: 10.1016/j.spinee.2017.09.011. Epub 2017 Sep 28.

  PMID: 28962909 BACKGROUND

• Sethi A, Emami B, Small W Jr, Thomas TO. Intraoperative Radiotherapy With INTRABEAM: Technical and Dosimetric Considerations. Front Oncol. 2018 Mar 26;8:74. doi: 10.3389/fonc.2018.00074. eCollection 2018.

  PMID: 29632850 BACKGROUND

• Bludau F, Welzel G, Reis T, Abo-Madyan Y, Sperk E, Schneider F, Clausen S, Ruder AM, Obertacke U, Ghaly MM, Wenz F, Giordano FA. Combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) versus external beam radiotherapy (EBRT) for painful vertebral metastases - a randomized phase III study. BMC Cancer. 2019 May 9;19(1):430. doi: 10.1186/s12885-019-5666-5.

  PMID: 31072314 BACKGROUND

• Bludau F, Winter L, Welzel G, Obertacke U, Schneider F, Wenz F, Ruder AM, Giordano FA. Long-term outcome after combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) for vertebral tumors. Radiat Oncol. 2020 Nov 12;15(1):263. doi: 10.1186/s13014-020-01715-z.

  PMID: 33183307 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Frank Giordano, MD

  Universitätsmedizin Mannheim

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Frederik Wenz

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 16, 2016
• Study Start: November 12, 2017
• Primary Completion: March 6, 2020
• Study Completion: March 6, 2020
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)