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

Not Applicable

Recruiting

• Conditions: Oligometastatic Disease; Toxicity Due to Radiotherapy; Oligoprogression; Quality of Life
• Interventions: Radiation: Multiple fraction SABR; Other: QoL reporting alone; Radiation: Single fraction SABR; Other: QoL reporting, symptom screen and healthcare provider intervention

• Registration Number: NCT05784428
• Lead Sponsor: British Columbia Cancer Agency

Brief 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.

Study Timeline

• Study First Submitted: 2023-02-28
• Study First Submitted QC: 2023-03-23
• Study First Posted: 2023-03-24
• Status Verified: 2024-07
• Study Start: 2025-04-16
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-04
• Primary Completion: 2034-03-30
• Study Completion: 2034-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 598

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

Waivers to inclusion criteria will NOT be allowed.

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Multiple fraction SABR (Arm 1)	Multiple fraction SABR	Participants randomized to this arm will receive multiple fraction SABR
Patient-reported outcome (PRO) collection : QoL reporting alone (Arm A)	QoL reporting alone	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).
Single fraction SABR (Arm 2)	Single fraction SABR	Participants randomized to this arm will receive single fraction SABR
QoL reporting and healthcare provider (HCP) intervention guided by symptom screen (Arm B)	QoL reporting, symptom screen and healthcare provider intervention	* 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

Primary Outcome Measures

Name	Time	Method
Adverse events	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
Change in patient-reported quality of life	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	Approximately at the end of year 5 of follow-up, at study completion	Time from randomization to death from any cause (exploratory)
Lesional control rate	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
Progression-free survival	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
Resource utilization	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

Trial Locations

Locations (2)

BC Cancer; 🇨🇦 Vancouver, British Columbia, Canada

BC Cancer - Victoria; 🇨🇦 Victoria, British Columbia, Canada