Ablative Radiosurgery vs Stereotactic RT in 5 Fractions With SIB for Oligometastatic Bone Lesions

NCT05679427 | Recruiting DMC

• 1 other identifier: ONES Trial
• Study Type: interventional
• Target: 307
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised prospective monoinstitutional study comparing radiosurgery at a total dose up to 24 Gy to five fraction stereotactic radiotherapy with simultaneous integrated boost (SIB) up to 50 Gy for the treatment of bone metastases in oligometastatic cancer treated with radical intent. At the end of the first 12 months from the start of the study an interim analysis will be performed taking into account all major endpoints for an initial evaluation of the study , with only an observational purpose, without subsequent protocol changes.

Conditions

Oligometastatic Disease

Keywords

SBRT; Simultaneous Integrated Boost; Oligometastatic Disease; Bone Metastases

Outcome Measures

Primary Outcomes (1)

• Local recurrence-free surival

  evaluation of the impact of stereotactic radiotherapy (one fraction versus fractionated) on local control of disease in terms of local recurrence free survival (LRFS) in patients with oligometastastic disease and at least one bone metastasis.

  3 years from the end of treatment

Secondary Outcomes (9)

• Acute and late local toxicity

  Changes form baseline at 3 years from the end of treatment

• Pain control

  Changes form baseline at 3 years from the end of treatment

• Overall survival

  3 years from the end of treatment

• Cancer Specific Survival

  3 years from the end of treatment

• Progression to polymetastatic disease

  3 years from the end of treatment

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Single fraction radiosurgery on bone metastases (21-24Gy x 1 fraction)

Radiation: radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively

Arm B

ACTIVE COMPARATOR

Multi-fractioned stereotactic ablative radiotherapy (5 fractions delivered in 5 consecutive working days) with SIB on bone metastases (5Gy x 5 fractions + SIB up to 40-50Gy)

Radiation: radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively

Interventions

radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively RADIATION

Two protocols of stereotactic ablative radiotherapy, in one vs five fractions ( the later with SIB) are compared

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Performance status ECOG ≤2
• Life expectancy \> 6 months according to Mizumoto criteria\*
• Oligometastatic disease (Total number of metastases from 1 to 5: both synchronous and metachronous with maximum involvement of three organs in total - lymph nodes, bones, lungs, liver, adrenal gland, brain- with known histology
• At least one bone metastasis treatable with SABR or SRS
• Each secondary localization (synchronous, metachronous or oligoprogressive) must be treated with radical intent.
• Patients may have received other anticancer treatments (surgery for initial site of disease or other metastases, chemotherapy, radiotherapy for other metastatic sites)

You may not qualify if:

• Sites of disease not eligible for stereotactic radiotherapy
• Serious medical comorbidities that preclude RT
• Overlap with a previously treated volume of radiotherapy
• Dimension greater than 5 cm for extra-cranial lesions.
• Size greater than 3 cm for brain lesions
• More than 1 brain metastases
• Clinical or radiological evidence of spinal cord compression or epidural tumor within 2mm of the spinal cord
• Radiological evidence of vertebral body fracture or involvement of more than 40% of the vertebral body
• Radiological evidence of cortical involvement in long bones
• Pregnant or breastfeeding women

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

San Raffaele Scientific Institute

Milan, MI, 20132, Italy

RECRUITING

Related Publications (20)

• Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available.

  PMID: 7799047 BACKGROUND

• Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49. doi: 10.1016/s0022-5223(97)70397-0.

  PMID: 9011700 BACKGROUND

• Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, Mendez Romero A, Nevens D, Palma D, Park C, Ricardi U, Scorsetti M, Yu J, Woodward WA. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020 Jul;148:157-166. doi: 10.1016/j.radonc.2020.04.003. Epub 2020 Apr 22.

  PMID: 32388150 BACKGROUND

• Lehrer EJ, Singh R, Wang M, Chinchilli VM, Trifiletti DM, Ost P, Siva S, Meng MB, Tchelebi L, Zaorsky NG. Safety and Survival Rates Associated With Ablative Stereotactic Radiotherapy for Patients With Oligometastatic Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2021 Jan 1;7(1):92-106. doi: 10.1001/jamaoncol.2020.6146.

  PMID: 33237270 BACKGROUND

• Zelefsky MJ, Yamada Y, Greco C, Lis E, Schoder H, Lobaugh S, Zhang Z, Braunstein S, Bilsky MH, Powell SN, Kolesnick R, Fuks Z. Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer. Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):672-679. doi: 10.1016/j.ijrobp.2021.01.004. Epub 2021 Jan 8.

  PMID: 33422612 BACKGROUND

• Ryu S, Jin R, Jin JY, Chen Q, Rock J, Anderson J, Movsas B. Pain control by image-guided radiosurgery for solitary spinal metastasis. J Pain Symptom Manage. 2008 Mar;35(3):292-8. doi: 10.1016/j.jpainsymman.2007.04.020. Epub 2008 Jan 22.

  PMID: 18215498 BACKGROUND

• Ryu S, Jin JY, Jin R, Rock J, Ajlouni M, Movsas B, Rosenblum M, Kim JH. Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery. Cancer. 2007 Feb 1;109(3):628-36. doi: 10.1002/cncr.22442.

  PMID: 17167762 BACKGROUND

• Zeng KL, Tseng CL, Soliman H, Weiss Y, Sahgal A, Myrehaug S. Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Spine Metastases: An Overview. Front Oncol. 2019 May 1;9:337. doi: 10.3389/fonc.2019.00337. eCollection 2019.

  PMID: 31119099 BACKGROUND

• Rusthoven KE, Kavanagh BD, Burri SH, Chen C, Cardenes H, Chidel MA, Pugh TJ, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol. 2009 Apr 1;27(10):1579-84. doi: 10.1200/JCO.2008.19.6386. Epub 2009 Mar 2.

  PMID: 19255320 BACKGROUND

• Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM, Dingemans AC, Fournier B, Hurkmans C, Lecouvet FE, Meattini I, Mendez Romero A, Ricardi U, Russell NS, Schanne DH, Scorsetti M, Tombal B, Verellen D, Verfaillie C, Ost P. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020 Jan;21(1):e18-e28. doi: 10.1016/S1470-2045(19)30718-1.

  PMID: 31908301 BACKGROUND

• Loi M, Alifano M, Scorsetti M, Nuyttens JJ, Livi L. Judging a Fish by Its Ability to Climb a Tree? A Call for Novel Endpoints in the Appraisal of Ablative Local Treatments of Oligometastatic Cancer. Oncologist. 2021 Jun;26(6):e1085-e1086. doi: 10.1002/onco.13747. Epub 2021 Apr 9.

  PMID: 33686724 BACKGROUND

• Poon I, Erler D, Dagan R, Redmond KJ, Foote M, Badellino S, Biswas T, Louie AV, Lee Y, Atenafu EG, Ricardi U, Sahgal A. Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis. JAMA Netw Open. 2020 Nov 2;3(11):e2026312. doi: 10.1001/jamanetworkopen.2020.26312.

  PMID: 33196810 BACKGROUND

• Buglione M, Jereczek-Fossa BA, Bonu ML, Franceschini D, Fodor A, Zanetti IB, Gerardi MA, Borghetti P, Tomasini D, Di Muzio NG, Oneta O, Scorsetti M, Franzese C, Romanelli P, Catalano G, Dell'Oca I, Beltramo G, Ivaldi GB, Laudati A, Magrini SM, Antognoni P; Italian Society of Radiotherapy and Clinical Oncology - Regional Group Lombardy (AIROL). Radiosurgery and fractionated stereotactic radiotherapy in oligometastatic/oligoprogressive non-small cell lung cancer patients: Results of a multi-institutional series of 198 patients treated with "curative" intent. Lung Cancer. 2020 Mar;141:1-8. doi: 10.1016/j.lungcan.2019.12.019. Epub 2020 Jan 3.

  PMID: 31926440 BACKGROUND

• Sindhu KK, Leiter A, Moshier E, Lin JY, Carroll E, Brooks D, Shimol JB, Eisenberg E, Gallagher EJ, Stock RG, Galsky MD, Buckstein M. Durable disease control with local treatment for oligoprogression of metastatic solid tumors treated with immune checkpoint blockade. Cancer Treat Res Commun. 2020;25:100216. doi: 10.1016/j.ctarc.2020.100216. Epub 2020 Oct 8.

  PMID: 33049542 BACKGROUND

• Gaertner J, Elsner F, Pollmann-Dahmen K, Radbruch L, Sabatowski R. Electronic pain diary: a randomized crossover study. J Pain Symptom Manage. 2004 Sep;28(3):259-67. doi: 10.1016/j.jpainsymman.2003.12.017.

  PMID: 15336338 BACKGROUND

• de Wit R, van Dam F, Hanneman M, Zandbelt L, van Buuren A, van der Heijden K, Leenhouts G, Loonstra S, Abu-Saad HH. Evaluation of the use of a pain diary in chronic cancer pain patients at home. Pain. 1999 Jan;79(1):89-99. doi: 10.1016/S0304-3959(98)00158-4.

  PMID: 9928781 BACKGROUND

• Mizumoto M, Harada H, Asakura H, Hashimoto T, Furutani K, Hashii H, Takagi T, Katagiri H, Takahashi M, Nishimura T. Prognostic factors and a scoring system for survival after radiotherapy for metastases to the spinal column: a review of 544 patients at Shizuoka Cancer Center Hospital. Cancer. 2008 Nov 15;113(10):2816-22. doi: 10.1002/cncr.23888.

  PMID: 18846565 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

• Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ, Movsas B, Kanner AA, Berk LB, Followill DS, Kachnic LA. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol. 2014 Mar-Apr;4(2):76-81. doi: 10.1016/j.prro.2013.05.001. Epub 2013 Jun 4.

  PMID: 24890347 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

MeSH Terms

Interventions

Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nadia G Di Muzio, Prof

  IRCCS San Raffaele, Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadia G Di Muzio, Prof.

CONTACT

+390226437643; dimuzio.nadia@hsr.it

Andrei Fodor, MD

CONTACT

+390226437634; fodor.andrei@hsr.it

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: Professor

Model Details: The sample size calculation is based on the Kaplan-Meier estimator and uses a log-rank test (Freedman, 1982; Machin et al., 2018). Assuming for the two groups a two-year LRFS of 95% and 85%, respectively, with alpha=0.05 and power of 80%, the total number needed to identify a significant difference between the two curves is 292 (test at 2 queues, 146 patients per group). Calculations were performed with software (PASS 2021, v21.0.3). Assuming a 5% dropout, we expect to enroll 15 more patients in total, thus reaching a final number of 307.

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: January 11, 2023
• Study Start: November 7, 2022
• Primary Completion: November 7, 2025
• Study Completion (Estimated): December 7, 2027
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Five years after the end of the study.
• Access Criteria: Requests to corresponding author, approved by Ethics Committee

Locations

IT (1)