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

June 20, 2023 updated by: Nadia Di Muzio, IRCCS San Raffaele

A Randomised, Prospective, Monoinstitutional Study of Ablative Radiosurgery vs Stereotactic Radiotherapy in 5 Fractions, With Simultaneous Integrated Boost, for the Treatment of Bone Lesions in Oligometastatic Disease

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study is interventional, homogeneous (performed in a single institution). Patient recruitment Patients who meet the inclusion criteria will be enrolled during the initial Radiation Oncology examination in our institution or during the multidisciplinary meeting.

Recruitment and selection The patients will be informed of the possibility to participate in the study. I pazienti verranno informati ella possibilità di accedere allo studio. After a careful verification of the inclusion and exclusion criteria, and precise description of the benefits, risks and procedure of the current study, the patient will be asked to sign the informed consent and subsequently randomised.

The following information will be collected for each patient, as is standard practice in our department: demographic data, clinical history, concomitant medical treatments, physical exam, blood exam, tumoral markers, diagnoses CT / Bone scintigraphy/ MRI/ PET and any other staging exam or post tumoral treatment re-evaluation performed.

Randomisation A centralized randomization, with closed envelopes, will be performed by a secretary not involved in the study.

Pre-treatment phase Each patient will undergo the simulation CT, in line with routine clinical practice, with immobilisation devices within 15 (+/- 5) days from the randomisation. The simulation CT will be performed in the Radiotherapy department, the MRI in the Radiology department.

Treatment phase The protocol treatment uses two radiotherapy regimens with ablative doses, which are already included in the daily clinical practice at San Raffaele Scientific Institute and many other national centers equipped with High Technology. The treatment machine will be randomly assigned, depending on the availability of slots for the timing required by the protocol.

The patients will be randomized at a 1:1 ratio between:

  • Arm A: radiosurgery ( in one fraction) to the bone metastases ( 21-24 Gy in 1 fraction)
  • Arm B: Multifractionated ablative stereotactic radiotherapy (5 fractions, one fraction per day, 5 consecutive weekdays) with SIB to the bone metastases (up to 40-50 Gy).

The treatment should be completed within 1 month from the CT simulation and within 45 (+/- 5) days from randomization (first visit).

Post-treatment phase:

Patients will be evaluated according to departmental clinical practice: at the first visit, at the end of the treatment and at follow-up visits at 3, 6, 12, 18, 24, 36 months from the end of radiotherapy with CT and/or Bone Scan and/or MRI and/or PET/CT based on the treated sites, on the histology of primary tumor, and by means of laboratory exams. Subsequent radiological images of laboratory analyses will be performed at the discretion of the radiation oncologist, based on symptoms or clinical findings. At every visit the anamnesis, physical examination, the CTCAE(Common Terminology Criteria for Adverse Events) toxicity evaluation will be performed and registered, together with any skeletal events, re-irradiation, other systemic therapy lines, or palliative treatment. The patient will fill in the Pain Diary and the quality of life questionnaires (EORTC QLQ-C30, QLQBM22, and EQ-5D-3L). The follow-up visits will be performed in the dedicated rooms of the Radiation Oncology department.

Study Type

Interventional

Enrollment (Estimated)

307

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • MI
      • Milan, MI, Italy, 20132
        • Recruiting
        • San Raffaele Scientific Institute
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A
Single fraction radiosurgery on bone metastases (21-24Gy x 1 fraction)
Radiation: radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively
Two protocols of stereotactic ablative radiotherapy, in one vs five fractions ( the later with SIB) are compared
Active Comparator: Arm B
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
Two protocols of stereotactic ablative radiotherapy, in one vs five fractions ( the later with SIB) are compared

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local recurrence-free surival
Time Frame: 3 years from the end of treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute and late local toxicity
Time Frame: Changes form baseline at 3 years from the end of treatment
Impact of the two treatments on the local radioinduced toxicity in terms of incidence in skeletal events and acute and late toxicity measured with the Common Terminology Criteria for Adverse Events v5.0 scale
Changes form baseline at 3 years from the end of treatment
Pain control
Time Frame: Changes form baseline at 3 years from the end of treatment
Pain control of symptomatic bone lesions measured through the variation of pain diary
Changes form baseline at 3 years from the end of treatment
Overall survival
Time Frame: 3 years from the end of treatment
Overall-surival
3 years from the end of treatment
Cancer Specific Survival
Time Frame: 3 years from the end of treatment
Cancer Specific Survival
3 years from the end of treatment
Progression to polymetastatic disease
Time Frame: 3 years from the end of treatment
Impact of the two treatments on the rate of progression to polymethastatic disease
3 years from the end of treatment
Adjusted disease-free survival
Time Frame: 3 years from the end of treatment
defined as the time between the end of radiotherapy and the date of disease progression (local or distant) or the start of therapy (systemic or palliative)
3 years from the end of treatment
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-C30
Time Frame: Changes from baseline at 3 years after the treatment
Quality-of-life assessed by EORTC-QLQ-C30 questionnaire
Changes from baseline at 3 years after the treatment
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-BM22
Time Frame: Changes from baseline at 3 years after the treatment
Quality-of-life assessed by EORTC-QLQ-BM22 questionnaire
Changes from baseline at 3 years after the treatment
Satisfaction assessed by EQ-5D-3L
Time Frame: Changes from baseline at 3 years after the treatment
Quality-of-life assessed by EQ-5D-3L questionnaire
Changes from baseline at 3 years after the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 7, 2022

Primary Completion (Estimated)

November 7, 2025

Study Completion (Estimated)

December 7, 2027

Study Registration Dates

First Submitted

December 1, 2022

First Submitted That Met QC Criteria

December 23, 2022

First Posted (Actual)

January 11, 2023

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 20, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • ONES Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the IRCCS San Raffaele Scientific Institute Ethics Committee.

IPD Sharing Time Frame

Five years after the end of the study.

IPD Sharing Access Criteria

Requests to corresponding author, approved by Ethics Committee

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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