Comparing single and multiple doses of radiation therapy for treating oligometastatic disease

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

This study is testing whether one dose or several doses of radiation therapy works better and is safer for people with oligometastatic disease, while also looking at how it affects their quality of life and costs.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 598 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: British Columbia Cancer Agency (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 13 sites (Kelowna, British Columbia and 12 other locations)
• Trial ID: NCT05784428 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of single fraction versus multiple fraction stereotactic ablative radiotherapy (SABR) for patients with oligometastatic disease. It aims to assess differences in toxicities, progression-free survival, quality of life, and cost-effectiveness between the two treatment approaches. Additionally, a subset of patients will explore the impact of healthcare provider-guided interventions on quality of life compared to standard questionnaire completion. The study will involve patient-reported outcomes and symptom tracking to enhance understanding of treatment effects.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with 1-5 oligometastatic or oligo-progressive lesions and a life expectancy of more than 6 months.

Not a fit: Patients with more than 5 metastatic lesions or those unable to complete electronic patient-reported outcomes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into optimizing radiation therapy for better patient outcomes and quality of life.

How similar studies have performed: Previous studies have shown promise in comparing single and multiple fraction radiation therapies, but this specific approach is novel in its comprehensive evaluation of quality of life and cost-effectiveness.

Eligibility criteria

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

Where this trial is running

Kelowna, British Columbia and 12 other locations

• BC Cancer — Kelowna, British Columbia, Canada (Recruiting)
• BC Cancer — Prince George, British Columbia, Canada (Recruiting)
• BC Cancer — Surrey, British Columbia, Canada (Recruiting)
• BC Cancer — Vancouver, British Columbia, Canada (Recruiting)
• BC Cancer - Victoria — Victoria, British Columbia, Canada (Not_yet_recruiting)
• Princess Margaret Cancer Centre | University Health Network — Toronto, Ontario, Canada (Recruiting)
• University Hospital Galway — Galway, Connacht, Ireland (Recruiting)
• St. Luke's Radiation Oncology Network — Dublin, Dublin, Ireland (Recruiting)
• Mater Private Hospital — Dublin, Leinster, Ireland (Recruiting)
• Beacon Hospital — Dublin, Leinster, Ireland (Recruiting)
• Cork University Hospital — Cork, Munster, Ireland (Recruiting)
• Bon Secours Radiotherapy Cork in Partnership with UPMC Hillman Cancer Centre — Cork, Munster, Ireland (Recruiting)
• UPMC Whitfield Hospital - Waterford — Waterford, Munster, Ireland (Recruiting)

Study contacts

• Principal investigator: Robert Olson, MD, MSc, FRCPC — BC Cancer - Prince George
• Study coordinator: Robert Olson, MD, MSC, FRCPC

Conditions Oligometastatic Disease; Oligoprogression; Toxicity Due to Radiotherapy; Quality of Life