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

Primary Purpose

Oligometastatic Disease

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively
Sponsored by
IRCCS San Raffaele
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oligometastatic Disease focused on measuring SBRT, Simultaneous Integrated Boost, Oligometastatic Disease, Bone Metastases

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • San Raffaele Scientific InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

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

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Acute and late local toxicity
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
Pain control
Pain control of symptomatic bone lesions measured through the variation of pain diary
Overall survival
Overall-surival
Cancer Specific Survival
Cancer Specific Survival
Progression to polymetastatic disease
Impact of the two treatments on the rate of progression to polymethastatic disease
Adjusted disease-free survival
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)
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-C30
Quality-of-life assessed by EORTC-QLQ-C30 questionnaire
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-BM22
Quality-of-life assessed by EORTC-QLQ-BM22 questionnaire
Satisfaction assessed by EQ-5D-3L
Quality-of-life assessed by EQ-5D-3L questionnaire

Full Information

First Posted
December 1, 2022
Last Updated
June 20, 2023
Sponsor
IRCCS San Raffaele
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1. Study Identification

Unique Protocol Identification Number
NCT05679427
Brief Title
Ablative Radiosurgery vs Stereotactic RT in 5 Fractions With SIB for Oligometastatic Bone Lesions
Acronym
ONES
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 7, 2022 (Actual)
Primary Completion Date
November 7, 2025 (Anticipated)
Study Completion Date
December 7, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oligometastatic Disease
Keywords
SBRT, Simultaneous Integrated Boost, Oligometastatic Disease, Bone Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
307 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
Single fraction radiosurgery on bone metastases (21-24Gy x 1 fraction)
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Radiation
Intervention Name(s)
radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively
Intervention Description
Two protocols of stereotactic ablative radiotherapy, in one vs five fractions ( the later with SIB) are compared
Primary Outcome Measure Information:
Title
Local recurrence-free surival
Description
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.
Time Frame
3 years from the end of treatment
Secondary Outcome Measure Information:
Title
Acute and late local toxicity
Description
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
Time Frame
Changes form baseline at 3 years from the end of treatment
Title
Pain control
Description
Pain control of symptomatic bone lesions measured through the variation of pain diary
Time Frame
Changes form baseline at 3 years from the end of treatment
Title
Overall survival
Description
Overall-surival
Time Frame
3 years from the end of treatment
Title
Cancer Specific Survival
Description
Cancer Specific Survival
Time Frame
3 years from the end of treatment
Title
Progression to polymetastatic disease
Description
Impact of the two treatments on the rate of progression to polymethastatic disease
Time Frame
3 years from the end of treatment
Title
Adjusted disease-free survival
Description
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)
Time Frame
3 years from the end of treatment
Title
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-C30
Description
Quality-of-life assessed by EORTC-QLQ-C30 questionnaire
Time Frame
Changes from baseline at 3 years after the treatment
Title
Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-BM22
Description
Quality-of-life assessed by EORTC-QLQ-BM22 questionnaire
Time Frame
Changes from baseline at 3 years after the treatment
Title
Satisfaction assessed by EQ-5D-3L
Description
Quality-of-life assessed by EQ-5D-3L questionnaire
Time Frame
Changes from baseline at 3 years after the treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadia G Di Muzio, Prof.
Phone
+390226437643
Email
dimuzio.nadia@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Andrei Fodor, MD
Phone
+390226437634
Email
fodor.andrei@hsr.it
Facility Information:
Facility Name
San Raffaele Scientific Institute
City
Milan
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadia G Di Muzio, Prof
Phone
+390226437643
Email
dimuzio.nadia@hsr.it
First Name & Middle Initial & Last Name & Degree
Fodor Andrei, M.D.
Phone
+390226437634
Email
fodor.andrei@hsr.it

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
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Ablative Radiosurgery vs Stereotactic RT in 5 Fractions With SIB for Oligometastatic Bone Lesions

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