Single vs. Multiple Fraction Trial of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastases/Progression

March 9, 2026 updated by: Robert Olson

Single vs. Multiple Fraction Non-Inferiority Trial of Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligo-metastases/Progression: SIMPLIFY-SABR-COMET

Stereotactic Ablative Radiotherapy (SABR) is a modern RT technique that delivers high doses of radiation to small tumor targets using highly conformal techniques, while trying to avoid healthy tissues and organs. However, SABR treatment requires increased planning, treatment time, cost and potential for higher toxicity due to the higher dose. The purpose of this study is to compare single fraction (SF) SABR vs. multiple fraction (MF) SABR in regards to toxicities, progression-free survival, quality of life (QoL), and cost-effectiveness. In a subset of patients, we will also compare patient QoL, hospitalization rates, and cost-effectiveness between patients who complete QoL questionnaires, record symptoms and receive healthcare provider-guided intervention vs. patients who complete QoL questionnaires only.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Radiation can be delivered in multiple fractions, or doses, and can take up to several weeks or months of treatment depending on the type of cancer. Radiation can also be offered in a single fraction. Both techniques have evidence for use in clinical care. Multiple fraction is offered to reduce the amount of radiation given at a single time that could reduce late toxicities. However, single fraction radiotherapy is more cost-effective and saves patient time. With this trial, we will compare single fraction vs. multiple fraction in regards to their impact on toxicity, progression-free survival: time from randomization to disease progression at any site or death, lesional control rate: lesion size post-SABR, quality of life and cost-effectiveness.

In a subset of sites, we will also investigate the impact of healthcare-provider guided intervention on quality of life. Questionnaires capture various symptoms such as pain, fatigue and information relating to physical, social, and mental wellbeing. This information can help shed light on patient experience and provide a better understanding of the effects of radiation therapy. In this trial, we will compare quality of life questionnaire completion, symptom reporting and healthcare-provider guided intervention vs. quality of life questionnaire completion alone, in regards to patient quality of life. Hospitalization rates and frequency of emergency department visits will also be investigated.

Sample size: The total sample size of 598 for this trial was calculated based on the primary endpoint of toxicity for the single vs. multiple fraction SABR randomization. Calculations were performed based on the results of the SABR-5 trial and our clinical judgement.

Quality Assurance: Radiation treatments are based on the current phase III SABR-COMET-3 trial and as per recent clinical evidence. All treatments will be planned as per protocol including computed tomography (CT) simulation, organs at risk contouring and undergo a quality assurance process.

For the subset of sites involved in the second randomization, training will be provided to patients on the use of Noona, a patient-reported outcome platform.

Study Type

Interventional

Enrollment (Estimated)

598

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

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada
      • Prince George, British Columbia, Canada, V2M 7E9
      • Surrey, British Columbia, Canada
      • Vancouver, British Columbia, Canada
        • Recruiting
        • BC Cancer
        • Contact:
      • Victoria, British Columbia, Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X6
        • Recruiting
        • Princess Margaret Cancer Centre | University Health Network
        • Principal Investigator:
          • Chiaojung Jillian Tsai
        • Contact:
  • Ireland
    • Connacht
      • Galway, Connacht, Ireland, H91 YR71
        • Recruiting
        • University Hospital Galway
        • Contact:
        • Principal Investigator:
          • Ronan McDermott
    • Dublin
      • Dublin, Dublin, Ireland, D06 E1C9
        • Recruiting
        • St. Luke's Radiation Oncology Network
        • Contact:
        • Principal Investigator:
          • Lorna Keenan
    • Leinster
      • Dublin, Leinster, Ireland, D18 AK68
        • Recruiting
        • Beacon Hospital
        • Contact:
        • Principal Investigator:
          • Alina Mihai
      • Dublin, Leinster, Ireland, D07 WKW8
        • Recruiting
        • Mater Private Hospital
        • Contact:
        • Principal Investigator:
          • Daniel Cagney
    • Munster
      • Cork, Munster, Ireland, T12 DV56
        • Recruiting
        • Bon Secours Radiotherapy Cork in partnership with UPMC Hillman Cancer Centre
        • Principal Investigator:
          • Paul Kelly
        • Contact:
      • Cork, Munster, Ireland, T12 DC4A
        • Recruiting
        • Cork University Hospital
        • Contact:
        • Principal Investigator:
          • Aisling Barry
      • Waterford, Munster, Ireland, X91 DH9W
        • Recruiting
        • UPMC Whitfield Hospital - Waterford
        • Contact:
        • Principal Investigator:
          • Ciara Lyons

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1-5 current oligometastatic or oligo-progressive lesions
  • Age 18 years or older
  • Able to provide informed consent
  • Able to complete electronic entry of patient reported outcomes and questionnaires independently or with assistance from a caregiver/family/friend/research staff using electronic methods after providing consent to email use.
  • Life expectancy > 6 months
  • Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Controlled primary tumor: defined as at least 3 months since original tumor treated radically, with no progression at primary site (can be considered controlled if no evidence of the primary tumour on imaging [e.g. primary unknown])
  • A history and physical examination, including ECOG performance status, performed within 6 weeks prior to enrollment
  • Patient has had a CT chest, abdomen and pelvis or PET-CT within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
  • Patient has had a nuclear bone scan (if no positron emission tomography-computed tomography [PET-CT]) within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
  • Patient has had CT or MRI brain imaging if primary has a propensity for central nervous system metastases (if deemed appropriate by the treating investigator) within 10 weeks prior to enrollment, and within 13 weeks prior to treatment.
  • For patients with known spine metastases, patient has had MRI spine imaging within 10 weeks prior to enrollment, and with 13 weeks prior to treatment.
  • If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has had an FDG (fluorodeoxyglucose) PET scan or CT (chest, abdomen, pelvis) and bone scan within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
  • If colorectal primary with rising Carcinoembryonic antigen (CEA), but equivocal imaging, patient has had an FDG PET scan within 10 weeks prior to enrollment, and within 13 weeks prior to treatment

  • Patient is judged able to:

    • Maintain a stable position during therapy
    • Tolerate immobilization device(s) that may be required to deliver SABR safely
  • Negative pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of RT start date

Exclusion Criteria:

  • Uncontrolled concurrent malignant cancer
  • Lesion in femoral bone requiring surgical fixation
  • No chemotherapy agents (cytotoxic, or molecularly targeted agents) will be used within the period of time commencing 1 week prior to radiation, lasting until 1 week after the last fraction. See section 5.3.3 regarding this criterion.
  • Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the gastrointestinal (GI) tract will receive radiotherapy, and connective tissue disorders such as lupus or scleroderma.
  • Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, similar biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases should be discussed with the local and study principal investigators (PIs).
  • Current malignant pleural effusion
  • Liver metastases located in the "Biliary no fly zone" defined for this trial as common biliary track, cystic duct and distal branches (1 cm) + 5 mm.
  • Inability to treat all sites of oligometastatic or oligoprogressive disease
  • Presence of brain metastases as the sole site of disease

  • Maximum size of 5 cm for lesions outside the brain, except:

    • Bone metastases over 5 cm may be included, if in the opinion of the local PI it can be treated safely (e.g. rib, scapula, pelvis)
  • Any brain metastasis > 3.5 cm in size or a total volume of brain metastases greater than 30 cc is excluded
  • Clinical or radiologic evidence of spinal cord compression. Patients can be eligible if surgical resection has been performed
  • Patients with spine instability as judged by a Spinal Instability Neoplastic Score (SINS) of >12
  • Dominant brain metastasis requiring surgical decompression
  • Surgical resection of all metastases (i.e. no lesion available to be treated with SABR)
  • Complete response to systemic therapy, defined as the absence of visible disease on imaging
  • Pregnant or breast feeding

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: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Multiple fraction SABR (Arm 1)
Participants randomized to this arm will receive multiple fraction SABR
Radiation: Multiple fraction SABR

Participants randomized to this arm will receive MF SABR:

Dose/Fractionation are as follows:

Lung: Greater than 2 cm from mediastinum or brachial plexus or if mandatory organ-at-risk (OAR) constraints are met: 48 Gy in 4 fractions (12 Gy/#), 54 Gy in 3 fractions (18 Gy/#), daily or every second day

Lung: Within 2 cm of mediastinum or brachial plexus 60 Gy in 8 fractions (7.5 Gy/#), 50 Gy in 5 fractions (10 Gy/#), daily

Bone: Any bone except spine: 35 Gy in 5 fractions (7 Gy/#), daily

Liver: 54 Gy in 3 fractions (18 Gy/#) or 5 fractions (10.8 Gy/#), daily or every second day

Spine: 24 Gy in 2 fractions (12 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily

Adrenal: 40 Gy in 5 fractions (8 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily

Lymph node/soft tissue: 40 Gy in 5 fractions (8 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily

Brain - dose per institutional policy for stereotactic lesions (no whole brain RT).
Experimental: Single fraction SABR (Arm 2)
Participants randomized to this arm will receive single fraction SABR
Radiation: Single fraction SABR

Participants randomized to this arm will receive SF SABR

Treatment recommendations are as follows:

Lung: Greater than 2 cm from mediastinum or brachial plexus or if mandatory OAR constraints are met: 30 Gy in 1 fraction

Lung: Within 2 cm of mediastinum or brachial plexus 20 Gy in 1 fraction

Bone, Spine, Adrenal, lymph node/soft tissue: 20 Gy in 1 fraction

Liver: 30 Gy in 1 fraction

Brain: dose as per institutional policy
Active Comparator: Patient-reported outcome (PRO) collection : QoL reporting alone (Arm A)
Participants will complete the EuroQoL-5Dimensions-5levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy-General (FACT-G) prior to each scheduled follow-up (FU).
Other: QoL reporting alone
Participants randomized to this arm will complete the EQ-5D-5L and FACT-G at baseline and each follow-up visit
Experimental: QoL reporting and healthcare provider (HCP) intervention guided by symptom screen (Arm B)
  • Patients complete EQ-5D-5L and FACT-G prior to each scheduled FU
  • Patient complete online adaptive symptom screen with HCP intervention, prior to each scheduled appointment
Other: QoL reporting, symptom screen and healthcare provider intervention
Participants randomized to this arm will complete the FACT,G, EQ-5D-5L, radiation-symptom screen and receive healthcare provider-guided intervention based on their symptom reports.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Occurrences and changes in grade 3 or higher adverse events related to treatment, according to CTCAE v5.0
At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Change in patient-reported quality of life
Time Frame: At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
As measured by the EQ-5D-5L. This questionnaire provides measures for mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It also includes a numbered scale from 0 to 100 where 100 means the best health one can imagine, and 0 means the worst health one can imagine.
At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Approximately at the end of year 5 of follow-up, at study completion
Time from randomization to death from any cause (exploratory)
Approximately at the end of year 5 of follow-up, at study completion
Lesional control rate
Time Frame: At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Rate is determined based on lesion size post-SABR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Progression-free survival
Time Frame: At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Time from randomization to disease progression at any site or death
At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Resource utilization
Time Frame: At 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Assessed via patient- and provider-reported hospitalization rates, frequency of emergency department visits, number of patients with systemic or radiation therapy post SABR treatment on trial
At 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

Collaborators and Investigators

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

Sponsor

Robert Olson

Collaborators

Princess Margaret Hospital, Canada
London Regional Cancer Program, Canada
Tom Baker Cancer Centre

Investigators

  • Principal Investigator: Robert Olson, MD, MSc, FRCPC, BC Cancer - Prince George

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)

April 16, 2025

Primary Completion (Estimated)

April 30, 2035

Study Completion (Estimated)

May 30, 2035

Study Registration Dates

First Submitted

February 28, 2023

First Submitted That Met QC Criteria

March 23, 2023

First Posted (Actual)

March 24, 2023

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • SIMPLIFY-SABR-COMET

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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