Single Fraction and Multifraction Arc-Based Radiotherapy for Painful Bone Metastases (SMART)
14. august 2026 oppdatert av: Balaji Subramanian Sitaraman, Oman Ministry of Health
The SMART Trial: A Randomised Feasibility Study Comparing Single Fraction and Multifraction Arc-Based Radiotherapy for Painful Bone Metastases
This prospective randomised pilot feasibility study will compare single-fraction radiotherapy (8 Gy × 1) with multifraction radiotherapy (20 Gy in 5 fractions) for the palliation of painful bone metastases.
The study will evaluate pain response at 4 weeks following radiotherapy, together with feasibility, treatment compliance, toxicity, pain flare, retreatment, patient convenience and resource utilisation.
The study will generate preliminary data to inform the design of a future definitive randomised trial.
Studieoversikt
Status
Har ikke rekruttert ennå
Intervensjon / Behandling
Detaljert beskrivelse
Single-fraction radiotherapy (SFRT) is an established standard treatment for palliation of painful bone metastases. However, multifraction radiotherapy (MFRT) continues to be widely used in clinical practice because of concerns regarding durability of pain control and retreatment. With the increasing use of modern arc-based radiotherapy techniques such as volumetric modulated arc therapy (VMAT), there is a need to evaluate whether single-fraction radiotherapy can provide effective pain palliation while reducing treatment burden and improving resource utilisation.
The SMART trial is a prospective, single-centre, randomised, open-label, parallel-group pilot feasibility study comparing VMAT-based SFRT (8 Gy in 1 fraction) with VMAT-based MFRT (20 Gy in 5 fractions) in patients with painful bone metastases, including spinal metastases.
Approximately 70 participants will be randomised in a 1:1 ratio to receive either SFRT or MFRT. Both treatment schedules will be delivered using VMAT with daily image-guided radiotherapy using cone-beam computed tomography (CBCT)-based image guidance.
Stratified block randomisation will be used according to the site of metastasis (spine versus non-spine) to maintain balance between the two treatment groups. Within each stratum, computer-generated variable block randomisation using block sizes of 4 and 6 will be used. Allocation will be concealed using sequentially numbered, opaque, sealed envelopes.
Pain will be assessed using the Numeric Rating Scale (NRS-11) and Wong-Baker FACES Pain Scale at baseline and during follow-up. Participants will be assessed at 2 weeks, 4 weeks and 12 weeks after radiotherapy.
The primary aim of this pilot study is to assess the feasibility of conducting a randomised controlled trial at the participating tertiary oncology centre. Feasibility will include recruitment, treatment completion, follow-up completion and completeness of study data.
The primary efficacy outcome will be overall pain response at 4 weeks following radiotherapy. Secondary outcomes will include pain response at other follow-up time points, retreatment rates, pain flare, treatment-related toxicity, patient convenience and resource utilisation.
The study is not powered to provide a definitive non-inferiority conclusion. A non-inferiority margin of 15% has been prespecified to guide estimation of the treatment effect and inform the design and sample size of a future definitive randomised trial. The primary efficacy analysis will compare overall pain response between the two treatment groups using the intention-to-treat population.
The study will generate preliminary feasibility and clinical outcome data to inform the design of a future definitive randomised controlled trial evaluating single-fraction versus multifraction radiotherapy for painful bone metastases.
Studietype
Intervensjonell
Registrering (Antatt)
70
Fase
- Ikke aktuelt
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Balaji Subramanian Sitaraman, MBBS, DNB
- Telefonnummer: +96871926769
- E-post: balaji.radonc@gmail.com
Studiesteder
-
-
Muḩāfaz̧at Masqaţ
-
Muscat, Muḩāfaz̧at Masqaţ, Oman, 100
- Royal Hospital
-
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
Inclusion Criteria:
- Age ≥18 years
- Histologically proven malignancy
- Radiological evidence of bone or spine metastases
- Pain score ≥4 on Numeric Rating Scale (NRS-11)
- ECOG Performance Status 0-3
- Life expectancy ≥3 months.
- Ability to provide written informed consent
Exclusion Criteria:
- Spinal cord compression requiring emergency therapy
- Previous radiotherapy to same site
- Unstable pathological fracture requiring surgery
- Pregnancy
- Inability to provide consent
- Oligometastatic bone metastases requiring Stereotactic Body Radiotherapy (SBRT)
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Single-Fraction Radiotherapy (SFRT)
Participants will receive VMAT-basd radiotherapy to painful none metastasis, a total dose of 8 Gy delivered in a single fraction using CBCT based imaging guidance.
|
VMAT-based external beam radiotherapy planned to deliver 8 Gy in a single fraction with CBCT-based image guidance for the palliation of painful bone metastasis
|
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Aktiv komparator: Multifraction Radiotherapy (MFRT)
Participants will receive VMAT-basd radiotherapy to painful none metastasis, a total dose of 20Gy delivered in Five fractions using daily CBCT based imaging guidance.
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VMAT-based external beam radiotherapy planned to deliver 20 Gy in Five fractions of 4 Gy each with daily CBCT-based image guidance for the palliation of painful bone metastasis
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of target sample recruited
Tidsramme: From study initiation through completion of the recruitment period.
|
The percentage of the planned target sample successfully recruited during the recruitment period.
Recruitment feasibility will be interpreted using predefined traffic-light criteria: Green ≥80% (feasibility achieved), Amber 70-79% (borderline feasibility requiring review), and Red <70% (feasibility not achieved and requiring review).
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From study initiation through completion of the recruitment period.
|
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Percentage of participants completing assigned radiotherapy
Tidsramme: From randomisation through completion of assigned radiotherapy.
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The percentage of randomised participants who complete the assigned radiotherapy treatment according to the study protocol.
Treatment completion feasibility will be interpreted using predefined traffic-light criteria: Green ≥90% (feasibility achieved), Amber 80-89% (borderline feasibility requiring review), and Red <80% (feasibility not achieved and requiring review).
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From randomisation through completion of assigned radiotherapy.
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Percentage of participants completing 3-month follow-up
Tidsramme: From randomisation through 3 months after radiotherapy.
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The percentage of randomised participants who complete the required study follow-up through 3 months after radiotherapy.
Follow-up feasibility will be interpreted using predefined traffic-light criteria: Green ≥80% (feasibility achieved), Amber 70-79% (borderline feasibility requiring review), and Red <70% (feasibility not achieved and requiring review).
|
From randomisation through 3 months after radiotherapy.
|
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Percentage of participants with complete required study data
Tidsramme: From study initiation through 3 months after radiotherapy.
|
The percentage of participants with complete required study data according to the study data collection requirements.
Data completeness will be interpreted using predefined traffic-light criteria: Green ≥90% (feasibility achieved), Amber 80-89% (borderline feasibility requiring review), and Red <80% (feasibility not achieved and requiring review).
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From study initiation through 3 months after radiotherapy.
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Percentage of participants with major protocol deviations
Tidsramme: From randomisation through 3 months after radiotherapy.
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The percentage of participants with major protocol deviations during the study.
A major protocol deviation is a significant departure from the study protocol that may affect participant safety, treatment allocation, assessment of the primary outcome, or validity of the study results.
Protocol adherence will be interpreted using predefined traffic-light criteria: Green <10% major protocol deviations (feasibility achieved), Amber 10-20% (borderline feasibility requiring review), and Red >20% (feasibility not achieved and requiring review).
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From randomisation through 3 months after radiotherapy.
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Percentage of participants achieving overall pain response at 4 weeks.
Tidsramme: 4 weeks after radiotherapy
|
Overall pain response will be assessed using the NRS-11 and analgesic use.
Pain response is defined as a reduction of at least 2 points in pain from baseline with no escalation in analgesic use.
The percentage of participants achieving pain response will be compared between the SFRT and MFRT groups.
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4 weeks after radiotherapy
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Percentage of participants requiring retreatment
Tidsramme: From completion of radiotherapy through 3 months after radiotherapy
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The percentage of participants requiring repeat radiotherapy to the treated sitefor persisten or recurrence of pain will be recorded and compared between the SFRT and MFRT groups.
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From completion of radiotherapy through 3 months after radiotherapy
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Percentage of participants experiencing pain flare
Tidsramme: From completion of radiotherapy through 10 days after radiotherapy.
|
Pain flare following radiotherapy will be recorded and compared between the SFRT and MFRT groups.
Pain flare is defined as increase in NRS pain score by ≥2 points without reduction in analgesic use, or Increase in analgesic requirement by ≥25% without improvement in pain score, followed by return to the baseline pain level or analgesic requirement within 10 days after radiotherapy.
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From completion of radiotherapy through 10 days after radiotherapy.
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Percentage of participants achieving overall pain response at 2 weeks and 3 months
Tidsramme: 2 weeks and 3 months after radiotherapy
|
Overall pain response will be assessed using the NRS-11 and analgesic use.
Pain response is defined as a reduction of at least 2 points in pain from baseline with no escalation in analgesic use.
The percentage of participants achieving pain response will be recorded at 2 weeks and 3 months after radiotherapy and compared between the SFRT and MFRT groups.
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2 weeks and 3 months after radiotherapy
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Change in analgesic requirement from baseline
Tidsramme: At 2 weeks, 4 weeks, and 3 months after radiotherapy
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Change in analgesic requirement from baseline will be assessed using the patient's analgesic consumption and expressed as oral morphine equivalent dose (OMED).
The change in analgesic requirement will be recorded and compared between the SFRT and MFRT groups.
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At 2 weeks, 4 weeks, and 3 months after radiotherapy
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of participants receiving radiotherapy to new painful metastatic sites
Tidsramme: From completion of radiotherapy through 3 months after radiotherapy
|
The number of participants who receive radiotherapy to new painful metastatic sites during the 3-month follow-up period will be recorded descriptively.
This outcome reflects the occurrence of new painful metastatic disease during follow-up and is not intended to assess the efficacy of SFRT versus MFRT.
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From completion of radiotherapy through 3 months after radiotherapy
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Balaji Subramanian Sitaraman, MBBS, DNB, Royal Hospital, Ministry of Health, Oman
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M 3rd, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005 Jun 1;97(11):798-804. doi: 10.1093/jnci/dji139.
- Sahgal A, Myrehaug SD, Siva S, Masucci GL, Maralani PJ, Brundage M, Butler J, Chow E, Fehlings MG, Foote M, Gabos Z, Greenspoon J, Kerba M, Lee Y, Liu M, Liu SK, Thibault I, Wong RK, Hum M, Ding K, Parulekar WR; trial investigators. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021 Jul;22(7):1023-1033. doi: 10.1016/S1470-2045(21)00196-0. Epub 2021 Jun 11.
- McDonald R, Chow E, Lam H, Rowbottom L, Soliman H. International patterns of practice in radiotherapy for bone metastases: A review of the literature. J Bone Oncol. 2014 Nov 7;3(3-4):96-102. doi: 10.1016/j.jbo.2014.10.003. eCollection 2014 Nov.
- Hird A, Chow E, Zhang L, Wong R, Wu J, Sinclair E, Danjoux C, Tsao M, Barnes E, Loblaw A. Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three canadian cancer centers. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):193-7. doi: 10.1016/j.ijrobp.2008.10.044. Epub 2009 Jan 23.
- Westhoff PG, de Graeff A, Monninkhof EM, Pomp J, van Vulpen M, Leer JW, Marijnen CA, van der Linden YM; Dutch Bone Metastasis Study Group. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases. Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):694-701. doi: 10.1016/j.ijrobp.2015.06.024. Epub 2015 Jun 20.
- BalajiSubramanian S, Sathiya K, Balaji K, Thirunavukarasu M, Phanikiran S, Rela M. Re-irradiation after stereotactic body radiotherapy for spine metastases from hepatocellular carcinoma: a case report. Rep Pract Oncol Radiother. 2021 Dec 30;26(6):1060-1065. doi: 10.5603/RPOR.a2021.0098. eCollection 2021.
- Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):112-24. doi: 10.1016/j.clon.2011.11.004. Epub 2011 Nov 29.
- Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Warlam-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999 Aug;52(2):101-9. doi: 10.1016/s0167-8140(99)00110-3.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Antatt)
1. september 2026
Primær fullføring (Antatt)
1. desember 2027
Studiet fullført (Antatt)
30. desember 2027
Datoer for studieregistrering
Først innsendt
8. august 2026
Først innsendt som oppfylte QC-kriteriene
14. august 2026
Først lagt ut (Faktiske)
19. august 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
19. august 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
14. august 2026
Sist bekreftet
1. august 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- MoH/CSR/26/32133
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
IPD-planbeskrivelse
Individual participant data will not be routinely shared with other researchers.
The study is a single-center feasibility study, and the collected data will be used for the approved study objectives and institutional research purposes.
Any data sharing, if required in the future, will be considered in accordance with institutional policies, ethical approval, participant confidentiality, and applicable regulations.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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