NCT05784428

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

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 598 (estimated)
• Sponsor: Robert Olson · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

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

• Oligometastatic Disease
• Oligoprogression
• Toxicity Due to Radiotherapy
• Quality of Life

Interventions

Type	Name	Description
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
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).
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
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.

Timeline

• Start date: 2025-04-16
• Primary completion: 2035-04-30
• Completion: 2035-05-30
• First posted: 2023-03-24
• Last updated: 2026-03-11

Locations

13 sites across 2 countries: Canada, Ireland