Bony M - Stereotactic Ablative Radiotherapy (SABR) of Bony Metastases in Patients With Oligometastatic Disease

Bony M - Stereotactic Ablative Radiotherapy (SABR) of Bony Metastases in Patients With Oligometastatic Disease - A Phase II Study

This is a prospective, investigator-initiated, phase II, multicentre-study, investigating the efficacy and toxicity of definitive SABR of osseous oligometastases, when pragmatically introduced into a daily clinical setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Bone Metastases; Oligometastatic Disease; Stereotactic Body Radiotherapy
• Intervention / Treatment: Radiation: SABR

Detailed Description

Patients with a histology or cytology proven non-hematological cancer and at least one lesion in the bones are eligible.

Patients with de novo- and induced oligometastatic disease, as well as patients with oligo-recurrence or oligo-progression disease can be included. A total of 67 patients will be enrolled.

The overall aim is to document long time follow-up in respect to local control rate, OS, PFS, rate of symptomatic skeletal event at the irradiated site(s), time to progression outside the radiation field at 1-, 2- and 5-years and acute/ late toxicities.

The primary endpoint is the rate of local control 1-year post SABR. Patients will have a CT scan and a clinical evaluation every 3 month after SABR according to the standard clinical follow-up program.

During the 1 year follow-up we also perform pain assessment (using the Numeric Pain Rating Scale), report the analgesic consumption and Quality of life (QoL) measured with EQ-5D-5L.

Two dose levels are offered with either 37.5 gy in 3 fractions or 30 gy in 3 fractions, prescribed to the GTV.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Aalborg Universitetshospital
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • København, Denmark, 2100
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Odense University Hospital
• Norway
  • Trondheim, Norway
    • St Olavs Universitetssykehus,
  • Ålesund, Norway, 6026
    • Alesund sjukehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histology or cytology proven non-haematological cancer.
• At least one lesion in the bones is required.
• ECOG performance status ≤ 2.
• ≥ 18 years old.
• Life expectancy > 6 months.
• GTV diameter ≤ 5 cm.
• In case of de novo OMD and OMD recurrence a maximum of 5 targets (including the primary tumour) in a maximum of 3 organ sites are allowed.
• In case of OPD * and induced OMD*2 only 3 metastases (including the primary tumour) are allowed.
• The metastatic lesion(s) must be visible on a CT- or MR- scan and suitable for treatment with SABR.
• All metastatic sites are treated or planned for ablative therapy (including surgery) - for OPD only the sites in progression is required to fulfil this criterion. • A baseline scan within 28 days of inclusion (CT or PET- CT).
• For spine/paraspinal targets, an MR scan is mandatory, if epidural growth cannot be precluded on the baseline CT scan.
• No curative intended treatment option available.
• An ablative strategy should be deemed clinically relevant and is at the discretion of the treating physician to decide.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patient cannot tolerate physical set up required for SABR.
• Uncontrolled intercurrent illness.
• Pregnancy.
• Bilsky score ≥ 1b. If the patient is treated with surgery, a pre-operative Bilsky score ≥ 1b is an exclusion criterion as well. See appendix A for Bilsky score.
• Presence of myelopathy from the target area.
• Candidate for surgical treatment (determined by the institutions clinical oncologist, neurosurgeon or orthopaedic surgeon).
• For spine/paraspinal lesions where epidural growth cannot be precluded on the baseline CT scan: patients for whom an MR scan is contraindicated.
• Mechanical instability and/or fracture risk *3.
• For spine disease, involvement of ≥ three contiguous vertebrae.
• Uncontrolled disease in respect to malignant pleural effusion, ascites, lymphangitic carcinomatosis, pleural carcinomatosis or peritoneal carcinomatosis.
• Patients with uncontrolled brain metastases.
• If the patient has received previous radiotherapy, the combined dose at the radiation site must not exceed the dose constraints according to Appendix B. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm; All recruited patients are treated with SABR.	Radiation: SABR; Two fractionation regimes are available (37.5 Gy in 3 fractions and 30.0 Gy in 3 fractions)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
local control rate (LC) at 1-year post SABR	Response evaluation is based on the interpretation of a experienced onco-radiologist and modifications from the MDACC response criteria's.	1-year post SABR

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Symptomatic Skeletal Event (SSE) at the irradiated site(s)	Symptomatic Skeletal Event (SSE) of the irradiated site is defined as a radiographically verification of fracture (vertebral or non-vertebral, pathological or non-pathological), within or adjacent to the PTV of the irradiated site. The fracture must co-exist with one of the	3-, 6-, 12- and 24-months post SBRT
Pain, change from baseline evaluated by "Numeric Pain Rating Scale (NPRS)"	Response categories is based on patient reported pain scores (NPRS). The 11- 9 Protocol version 1.1, 01052020. Stereotactic ablative radiotherapy (SABR) of bony metastases in patients with oligometastatic disease - A phase II study point NPRS ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable").	Measured at 2-, 12-, 24-, 36- and 52-weeks post SBRT
NCI CTCAE ≥ grade 3 toxicity	Cummulated fraction of patients, who encounter one or more ≥ grade 3 NCI CTCAE toxicity within the first 3-months after SBRT.	Measured at 2-, 12-weeks post SBRT
NCI CTCAE ≥ grade 3 late toxicity	Cummulated fraction of patients, who encounter one or more ≥ grade 3 NCI CTCAE toxicity from 3-months and onward after SBRT including patients who have unresolved early toxicity (encontered within the first 3-months), that is not resolved at the 24-weeks follow-up.	Measured at 3-, 6-, 12- and 24-months post SBRT
Local progression free survival	Local progression free survival is defined as time from inclusion until progression of the irradiated lesion. Patients are not censored from analysis in case of new lesions outside the irradiated volume. The irradiated volume is defined as, within or adjacent to the PTV. Local progression free survival is reported as a continuos variable.	continuous within 2-years post SBRT
Progression-free survival (PFS)	Progression-free survival is defined as time from inclusion until disease progression or death following symptoms/interventions: progression in pain (according to definition in section 3.5), development of neurological symptoms/ symptomatic spinal cord compression or a need for surgical intervention/ reirradiation. It should be concluded from the treating physician that the symptom/intervention is a result of the fracture. Vertebral fractures include end plate-only fractures. Analysis is done at a lesion level, lesion by lesion. Patients with a pathological fracture before the radiation therapy, will not be included for analysis	Continuous and at 3-, 6-, 12- and 24-months post SBRT
Time to progression (TTP) outside the radiation field	Time to progression outside the radiation field is defined, as the time from inclusion until progression outside the radiation field, determined by a CT -, MR -, or PET-CT - scan. Outside the radiation field is defined as outside and not adjacent to the PTV.	Continuous and at 3-, 6-, 12- and 24-months post SBRT
Overall survival (OS)	OS is defined as time from inclusion until death from any cause	continuous till 2-year post SABR
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in mobility using the 5-level system in EQ-5D-5L	at 3-, 6-, 12- and 24-months post SBRT
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in self-care score using the 5-level system in EQ-5D-5L	at 3-, 6-, 12- and 24-months post SBRT
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in usual activities score using the 5-level system in EQ-5D-5L.	at 3-, 6-, 12- and 24-months post SBRT
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in pain/discomfort score using the 5-level system in EQ-5D-5L.	at 3-, 6-, 12- and 24-months post SBRT
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in anxiety/depression score using the 5-level system in EQ-5D-5L.	at 3-, 6-, 12- and 24-months post SBRT
Quality of life (QoL) measured with EQ-5D-5L.	Change from baseline in self assessed EQ visual analogue scale in EQ-5D-5L	at 3-, 6-, 12- and 24-months post SBRT

Collaborators and Investigators

• Sponsor: Gitte Fredberg Persson MD PhD
• Investigators: Principal Investigator: Gitte Persson, Hospital of Herlev and Gentifte

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): January 13, 2023
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: H-19039071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No