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

NCT ID: NCT05784428

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

598 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-16

Study Completion Date

2035-05-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Oligometastatic Disease Oligoprogression Toxicity Due to Radiotherapy Quality of Life

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

This study is a phase III multicentre randomized trial. All participants will be randomized in a 1:1 ratio between multiple fraction SABR (Arm 1) vs. single fraction SABR (Arm 2). Patients will be stratified by systemic therapy within the last 2 weeks (yes/no); number of sites to be treated (1 vs. multiple) and SABR to the abdominal/pelvic site (yes/no).

BC Cancer sites will also participate in the second randomization. Participants will be randomized in a 1:1 ratio to QoL reporting alone via FACT-G and EQ-5D-5L (Arm A) vs. QoL reporting and patient-reported outcome (PRO) symptom screen with healthcare provider intervention (Arm B). Patients will be further stratified by the criteria for the 1st randomization as as well as sex.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Multiple fraction SABR (Arm 1)

Participants randomized to this arm will receive multiple fraction SABR

Group Type ACTIVE_COMPARATOR

Multiple fraction SABR

Intervention Type RADIATION

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).

Single fraction SABR (Arm 2)

Participants randomized to this arm will receive single fraction SABR

Group Type EXPERIMENTAL

Single fraction SABR

Intervention Type RADIATION

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

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).

Group Type ACTIVE_COMPARATOR

QoL reporting alone

Intervention Type OTHER

Participants randomized to this arm will complete the EQ-5D-5L and FACT-G at baseline and each follow-up visit

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

Group Type EXPERIMENTAL

QoL reporting, symptom screen and healthcare provider intervention

Intervention Type OTHER

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.

Interventions

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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

Intervention Type 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).

Intervention Type RADIATION

QoL reporting alone

Participants randomized to this arm will complete the EQ-5D-5L and FACT-G at baseline and each follow-up visit

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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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 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
* 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)
* Pregnant or breast feeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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London Regional Cancer Program, Canada

OTHER

Sponsor Role collaborator

Tom Baker Cancer Centre

OTHER

Sponsor Role collaborator

Princess Margaret Hospital, Canada

OTHER

Sponsor Role collaborator

Robert Olson

OTHER

Sponsor Role lead

Responsible Party

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Robert Olson

Radiation Oncologist

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Robert Olson, MD, MSc, FRCPC

Role: PRINCIPAL_INVESTIGATOR

BC Cancer - Prince George

Locations

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BC Cancer

Surrey, British Columbia, Canada

Site Status NOT_YET_RECRUITING

BC Cancer

Vancouver, British Columbia, Canada

Site Status RECRUITING

BC Cancer - Victoria

Victoria, British Columbia, Canada

Site Status NOT_YET_RECRUITING

Princess Margaret Cancer Centre | University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

University Hospital Galway

Galway, Connacht, Ireland

Site Status RECRUITING

BC Cancer

Prince George, British Columbia, Canada

Site Status RECRUITING

BC Cancer

Kelowna, British Columbia, Canada

Site Status RECRUITING

St. Luke's Radiation Oncology Network

Dublin, Dublin, Ireland

Site Status RECRUITING

Mater Private Hospital

Dublin, Leinster, Ireland

Site Status RECRUITING

Beacon Hospital

Dublin, Leinster, Ireland

Site Status RECRUITING

Cork University Hospital

Cork, Munster, Ireland

Site Status RECRUITING

Bon Secours Radiotherapy Cork in Partnership with UPMC Hillman Cancer Centre

Cork, Munster, Ireland

Site Status RECRUITING

UPMC Whitfield Hospital - Waterford

Waterford, Munster, Ireland

Site Status RECRUITING

Countries

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Canada Ireland

Central Contacts

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Robert Olson, MD, MSC, FRCPC

Role: CONTACT

250-645-7300

Jordanna Laing, MSc

Role: CONTACT

250-645-7300

Facility Contacts

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Benjamin Mou, MD

Role: primary

250-712-3900

Robert A Olson, MD

Role: primary

2506457300

Jordanna Laing

Role: backup

2506457300

Devin Schellenberg, MD

Role: primary

604-930-2098

Mitchell Liu, MD

Role: primary

6048776000

Boris Valev, MD

Role: primary

250-519-5500

Yoona Shin

Role: primary

416-946-4558

Helen McLoughlin

Role: primary

091 542600

Roisin O'Maolalai

Role: primary

0035314065458

Lisa Scahill

Role: primary

+353 (1) 8034831

Roisin Conaty

Role: primary

353 1 293 6600

Murtaza Gangardiwala

Role: primary

021 4234807

Erica Bennett

Role: primary

+353 21-486-11

Erica Bennett

Role: primary

References

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Reference Type DERIVED
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Other Identifiers

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SIMPLIFY-SABR-COMET

Identifier Type: -

Identifier Source: org_study_id

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