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

Not Applicable
Recruiting
Conditions
Oligometastatic Disease
Interventions
Radiation: radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively
Registration Number
NCT05679427
Lead Sponsor
IRCCS San Raffaele
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
307
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm Aradiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectivelySingle fraction radiosurgery on bone metastases (21-24Gy x 1 fraction)
Arm Bradiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectivelyMulti-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)
Primary Outcome Measures
NameTimeMethod
Local recurrence-free surival3 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.

Secondary Outcome Measures
NameTimeMethod
Pain controlChanges form baseline at 3 years from the end of treatment

Pain control of symptomatic bone lesions measured through the variation of pain diary

Adjusted disease-free survival3 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)

Satisfaction assessed by EQ-5D-3LChanges from baseline at 3 years after the treatment

Quality-of-life assessed by EQ-5D-3L questionnaire

Overall survival3 years from the end of treatment

Overall-surival

Acute and late local toxicityChanges 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

Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-BM22Changes from baseline at 3 years after the treatment

Quality-of-life assessed by EORTC-QLQ-BM22 questionnaire

Cancer Specific Survival3 years from the end of treatment

Cancer Specific Survival

Progression to polymetastatic disease3 years from the end of treatment

Impact of the two treatments on the rate of progression to polymethastatic disease

Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-C30Changes from baseline at 3 years after the treatment

Quality-of-life assessed by EORTC-QLQ-C30 questionnaire

Trial Locations

Locations (1)

San Raffaele Scientific Institute

🇮🇹

Milan, MI, Italy

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