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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03862911




Registration number
NCT03862911
Ethics application status
Date submitted
8/02/2019
Date registered
5/03/2019
Date last updated
9/09/2020

Titles & IDs
Public title
Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer
Scientific title
Phase III Randomized Controlled Trial and Economic Evaluation of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer (SABR-COMET-3)
Secondary ID [1] 0 0
SABR-COMET-3
Universal Trial Number (UTN)
Trial acronym
SABR-COMET-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - palliative radiotherapy
Treatment: Other - Stereotactic ablative radiotherapy

Active Comparator: Standard of Care Treatment (Arm 1) - Standard of care, palliative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist

Experimental: Stereotactic Arm (Arm 2) - Stereotactic ablative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist


Treatment: Other: palliative radiotherapy
Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Patients in this arm should not receive stereotactic doses or radiotherapy boosts. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.

Treatment: Other: Stereotactic ablative radiotherapy
Lung:
Tumors 5 cm or less surrounded by lung parenchyma 48 Gy/4#, or 54 Gy/3#, daily or every second day Within 2 cm of mediastinum or brachial plexus 60 Gy/8#, daily
Bone: Any bone 35 Gy/5#, or 24 Gy/2#, daily Brain: Stereotactic lesions (no whole brain RT) <2cm 20-24 Gy/1#, once 2-3 cm 18 Gy/1#, once Metastases only: 35Gy/5# to PTV, daily Whole brain + Mets: 35Gy to metastases, daily 20 Gy whole brain, daily Liver: 54 Gy/3#, every second day Adrenal: 40 Gy/5#, daily Lymph Node: 40 Gy/5#, daily

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival - Time from randomization to death from any cause
Timepoint [1] 0 0
At approximately end of year 5 (study completion)
Secondary outcome [1] 0 0
Side effects - Occurrences of grade 2 or higher adverse events
Timepoint [1] 0 0
At 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Secondary outcome [2] 0 0
Progression-free survival (PFS) - Time from randomization to disease progression at any site or death.
Timepoint [2] 0 0
At 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Secondary outcome [3] 0 0
Patient-reported quality of life (QoL) - Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire
Timepoint [3] 0 0
At baseline, 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Secondary outcome [4] 0 0
Health-related quality of life (HRQoL) questionnaire - EuroQOL Group EQ-5D-5L
Timepoint [4] 0 0
At baseline, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Secondary outcome [5] 0 0
Resource Utilization (Patient and Provider Reported) - Number of hospital admissions, ER visits, systemic or radiation therapy
Timepoint [5] 0 0
At 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Secondary outcome [6] 0 0
Correlation between candidate biomarkers of oligometastatic disease (blood-derived) and oncologic outcomes - CTC and ctDNA Enumeration
Timepoint [6] 0 0
At baseline, 3 months, and disease progression or study completion (Year 5)

Eligibility
Key inclusion criteria
- Total number of metastases of 1-3

- Age 18 or older

- Willing to provide informed consent

- ECOG score 0-2

- Life expectancy >6 months

- Histologically confirmed malignancy with metastatic disease detected on imaging.
Biopsy of metastasis is preferred, but not required.

- Controlled primary tumor

- defined as: at least 3 months since original tumor treated definitively, with no
progression at primary site (can be considered controlled if no evidence of the
primary tumour on imaging)

- A history and physical exam, including ECOG performance status, performed within 6
weeks prior to trial enrollment

- Not suitable for resection at all sites or decline surgery

- Patient has had a CT chest, abdomen and pelvis or PET-CT within 8 weeks of enrollment,
and with 12 weeks of treatment

- Patient has had a nuclear bone scan (if no PET-CT) within 8 weeks of enrollment, and
with 12 weeks of treatment

- If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has
had an FDG PET scan or CT (chest, abdomen, pelvis) and bone scan within 8 weeks of
enrollment, and with 12 weeks of treatment

- If colorectal primary with rising CEA, but equivocal imaging, patient has had an FDG
PET scan within 8 weeks of enrollment, and with 12 weeks of treatment

- Patient has had CT or MRI brain imaging if primary has a propensity for CNS metastasis
within 8 weeks of enrollment, and with 12 weeks of 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 Women of Child-Bearing potential (WOCB) within 4 weeks of
RT start date

- Complete Blood Count (CBC)

- Patient is able and willing to complete the quality of life questionnaires, and other
assessments that are a part of this study, using REDCap and therefore has provided
their email address on the informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous SABR to the lesion(s)

- Lesion in femoral bone requiring surgical fixation

- No chemotherapy agents (cytotoxic, or molecularly targeted agents) will be used within
the period of time commencing 2 weeks prior to radiation, lasting until 1 week after
the last fraction for patients randomized to SABR.

- Serious medical comorbidities precluding radiotherapy. These include interstitial lung
disease in patients requiring thoracic radiation, Crohn's disease in patients where
the 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 conventional radiation previously, biological effective dose
calculations should be used to equate previous doses to the tolerance doses listed
below. All such cases should be discussed with one of the study PIs.

- Malignant pleural effusion

- History of poor lung function (if treating near lung)

- History of poor liver function (if treating near liver)

- Inability to treat all sites of disease

- Maximum size of 6 cm for lesions outside the brain, except:

- Bone metastases over 6 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 cm in size or a total volume of brain metastases greater
than 30 cc.

- Clinical or radiologic evidence of spinal cord compression, or epidural tumor within
<2 mm of the spinal cord. Patients can be eligible if surgical resection has been
performed, but the surgical site counts toward the total of up to 3 metastases.

- Dominant brain metastasis requiring surgical decompression

- Pregnant or breast feeding women

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
British Columbia
Country [2] 0 0
Canada
State/province [2] 0 0
Nova Scota
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Scotland
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Glasgow

Funding & Sponsors
Primary sponsor type
Other
Name
British Columbia Cancer Agency
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
London Regional Cancer Program, Canada
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Alfred
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Beacon Hospital, Ireland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Edinburgh Cancer Center, Scotland
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Metro South Hospital and Health Service via Princess Alexandra Hospital, Australia
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Beatson West of Scotland Cancer Center
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Cancer Trials Ireland
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
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. SABR is non-invasive
and delivered on an outpatient basis. The purpose of this study is to compare the effect of
SABR, relative to standard of care (SOC) alone, on overall survival, progression-free
survival, toxicity, and quality of life. An integrated economic evaluation will determine the
cost per quality of life year gained using SABR (vs. SOC) and a translational component will
enable identification of predictive/prognostic biomarkers of the oligometastatic state.
Trial website
https://clinicaltrials.gov/show/NCT03862911
Trial related presentations / publications
Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10.
Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49.
Hong JC, Ayala-Peacock DN, Lee J, Blackstock AW, Okunieff P, Sung MW, Weichselbaum RR, Kao J, Urbanic JJ, Milano MT, Chmura SJ, Salama JK. Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLoS One. 2018 Apr 12;13(4):e0195149. doi: 10.1371/journal.pone.0195149. eCollection 2018.
Primrose J, Treasure T, Fiorentino F. Lung metastasectomy in colorectal cancer: is this surgery effective in prolonging life? Respirology. 2010 Jul;15(5):742-6. doi: 10.1111/j.1440-1843.2010.01759.x. Epub 2010 Apr 23.
Palma DA, Salama JK, Lo SS, Senan S, Treasure T, Govindan R, Weichselbaum R. The oligometastatic state - separating truth from wishful thinking. Nat Rev Clin Oncol. 2014 Sep;11(9):549-57. doi: 10.1038/nrclinonc.2014.96. Epub 2014 Jun 24. Review.
Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018 Jan 11;4(1):e173501. doi: 10.1001/jamaoncol.2017.3501. Epub 2018 Jan 11.
Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.
Ruers T, Van Coevorden F, Punt CJ, Pierie JE, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Folprecht G, Van Cutsem E, Ducreux M, Nordlinger B; European Organisation for Research and Treatment of Cancer (EORTC); Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Inst. 2017 Sep 1;109(9). doi: 10.1093/jnci/djx015.
Ruers T, Punt C, Van Coevorden F, Pierie JPEN, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Van Cutsem E, Lutz MP, Nordlinger B; EORTC Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012 Oct;23(10):2619-2626. doi: 10.1093/annonc/mds053. Epub 2012 Mar 19.
Cheruvu P, Metcalfe SK, Metcalfe J, Chen Y, Okunieff P, Milano MT. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer. Radiat Oncol. 2011 Jun 30;6:80. doi: 10.1186/1748-717X-6-80.
Rava P, Leonard K, Sioshansi S, Curran B, Wazer DE, Cosgrove GR, Norén G, Hepel JT. Survival among patients with 10 or more brain metastases treated with stereotactic radiosurgery. J Neurosurg. 2013 Aug;119(2):457-62. doi: 10.3171/2013.4.JNS121751. Epub 2013 May 10.
Ritter TA, Matuszak M, Chetty IJ, Mayo CS, Wu J, Iyengar P, Weldon M, Robinson C, Xiao Y, Timmerman RD. Application of Critical Volume-Dose Constraints for Stereotactic Body Radiation Therapy in NRG Radiation Therapy Trials. Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):34-36. doi: 10.1016/j.ijrobp.2017.01.204.
De Oliveira C, Pataky R, Bremner KE, Rangrej J, Chan KK, Cheung WY, Hoch JS, Peacock S, Krahn MD. Estimating the Cost of Cancer Care in British Columbia and Ontario: A Canadian Inter-Provincial Comparison. Healthc Policy. 2017 Feb;12(3):95-108.
Devlin NJ, Krabbe PF. The development of new research methods for the valuation of EQ-5D-5L. Eur J Health Econ. 2013 Jul;14 Suppl 1:S1-3. doi: 10.1007/s10198-013-0502-3.
Leggett LE, Khadaroo RG, Holroyd-Leduc J, Lorenzetti DL, Hanson H, Wagg A, Padwal R, Clement F. Measuring Resource Utilization: A Systematic Review of Validated Self-Reported Questionnaires. Medicine (Baltimore). 2016 Mar;95(10):e2759. doi: 10.1097/MD.0000000000002759.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Olson, MD, MSc
Address 0 0
Country 0 0
Phone 0 0
250-645-7300
Fax 0 0
Email 0 0
rolson2@bccancer.bc.ca
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03862911