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

NCT05784428 | Recruiting DMC

• 1 other identifier: SIMPLIFY-SABR-COMET
• Study Type: interventional
• Target: 598
• Locations: 2 countries
• Sites: 13

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Occurrences and changes in grade 3 or higher adverse events related to treatment, according to CTCAE v5.0

  At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

• Change in patient-reported quality of life

  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.

  At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

Secondary Outcomes (4)

• Lesional control rate

  At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

• Progression-free survival

  At 6 weeks, 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

• Overall survival

  Approximately at the end of year 5 of follow-up, at study completion

• Resource utilization

  At 3 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months

Study Arms (4)

Multiple fraction SABR (Arm 1)

ACTIVE COMPARATOR

Participants randomized to this arm will receive multiple fraction SABR

Radiation: Multiple fraction SABR

Single fraction SABR (Arm 2)

EXPERIMENTAL

Participants randomized to this arm will receive single fraction SABR

Radiation: Single fraction SABR

Patient-reported outcome (PRO) collection : QoL reporting alone (Arm A)

ACTIVE COMPARATOR

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).

Other: QoL reporting alone

QoL reporting and healthcare provider (HCP) intervention guided by symptom screen (Arm B)

EXPERIMENTAL

* 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

Other: QoL reporting, symptom screen and healthcare provider intervention

Interventions

Single fraction SABR 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

Single fraction SABR (Arm 2)

QoL reporting alone OTHER

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

Patient-reported outcome (PRO) collection : QoL reporting alone (Arm A)

Multiple fraction SABR 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).

Multiple fraction SABR (Arm 1)

QoL reporting, symptom screen and healthcare provider intervention 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.

QoL reporting and healthcare provider (HCP) intervention guided by symptom screen (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Robert Olson: lead
• London Regional Cancer Program, Canada: collaborator
• Tom Baker Cancer Centre: collaborator
• Princess Margaret Hospital, Canada: collaborator

Study Sites (13)

BC Cancer

Kelowna, British Columbia, Canada

RECRUITING

BC Cancer

Prince George, British Columbia, V2M 7E9, 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, M5G 1X6, Canada

RECRUITING

University Hospital Galway

Galway, Connacht, H91 YR71, Ireland

RECRUITING

St. Luke's Radiation Oncology Network

Dublin, Dublin, D06 E1C9, Ireland

RECRUITING

Mater Private Hospital

Dublin, Leinster, D07 WKW8, Ireland

RECRUITING

Beacon Hospital

Dublin, Leinster, D18 AK68, Ireland

RECRUITING

Cork University Hospital

Cork, Munster, T12 DC4A, Ireland

RECRUITING

Bon Secours Radiotherapy Cork in Partnership with UPMC Hillman Cancer Centre

Cork, Munster, T12 DV56, Ireland

RECRUITING

UPMC Whitfield Hospital - Waterford

Waterford, Munster, X91 DH9W, Ireland

RECRUITING

Related Publications (13)

• Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available.

  PMID: 7799047 BACKGROUND

• Patel PH, Palma D, McDonald F, Tree AC. The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively? Clin Oncol (R Coll Radiol). 2019 Dec;31(12):824-833. doi: 10.1016/j.clon.2019.05.015. Epub 2019 Jun 8.

  PMID: 31182289 BACKGROUND

• Nguyen TK, Chin L, Sahgal A, Dagan R, Eppinga W, Guckenberger M, Kim JH, Lo SS, Redmond KJ, Siva S, Stish BJ, Chan R, Lawrence L, Lau A, Tseng CL. International Multi-institutional Patterns of Contouring Practice and Clinical Target Volume Recommendations for Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):351-360. doi: 10.1016/j.ijrobp.2021.09.004. Epub 2021 Sep 9.

  PMID: 34509549 BACKGROUND

• Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, Sheehan J, Gerszten PC, Chang E, Gibbs I, Soltys S, Sahgal A, Deasy J, Flickinger J, Quader M, Mindea S, Yamada Y. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e597-605. doi: 10.1016/j.ijrobp.2012.03.009. Epub 2012 May 19.

  PMID: 22608954 BACKGROUND

• Redmond KJ, Robertson S, Lo SS, Soltys SG, Ryu S, McNutt T, Chao ST, Yamada Y, Ghia A, Chang EL, Sheehan J, Sahgal A. Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine. Int J Radiat Oncol Biol Phys. 2017 Jan 1;97(1):64-74. doi: 10.1016/j.ijrobp.2016.09.014. Epub 2016 Sep 17.

  PMID: 27843035 BACKGROUND

• Dunne EM, Sahgal A, Lo SS, Bergman A, Kosztyla R, Dea N, Chang EL, Chang UK, Chao ST, Faruqi S, Ghia AJ, Redmond KJ, Soltys SG, Liu MC. International consensus recommendations for target volume delineation specific to sacral metastases and spinal stereotactic body radiation therapy (SBRT). Radiother Oncol. 2020 Apr;145:21-29. doi: 10.1016/j.radonc.2019.11.026. Epub 2019 Dec 23.

  PMID: 31874346 BACKGROUND

• Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.

  PMID: 21479777 BACKGROUND

• Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017

  BACKGROUND

• Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993 Mar;11(3):570-9. doi: 10.1200/JCO.1993.11.3.570.

  PMID: 8445433 BACKGROUND

• Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, Bruner DW, Cleeland CS, Sloan JA, Chilukuri R, Baumgartner P, Denicoff A, St Germain D, O'Mara AM, Chen A, Kelaghan J, Bennett AV, Sit L, Rogak L, Barz A, Paul DB, Schrag D. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014 Sep 29;106(9):dju244. doi: 10.1093/jnci/dju244. Print 2014 Sep.

  PMID: 25265940 BACKGROUND

• Basch E, Deal AM, Kris MG, Scher HI, Hudis CA, Sabbatini P, Rogak L, Bennett AV, Dueck AC, Atkinson TM, Chou JF, Dulko D, Sit L, Barz A, Novotny P, Fruscione M, Sloan JA, Schrag D. Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. J Clin Oncol. 2016 Feb 20;34(6):557-65. doi: 10.1200/JCO.2015.63.0830. Epub 2015 Dec 7.

  PMID: 26644527 BACKGROUND

• Olson R, Mathews L, Liu M, Schellenberg D, Mou B, Berrang T, Harrow S, Correa RJM, Bhat V, Pai H, Mohamed I, Miller S, Schneiders F, Laba J, Wilke D, Senthi S, Louie AV, Swaminath A, Chalmers A, Gaede S, Warner A, de Gruijl TD, Allan A, Palma DA. Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 2020 May 5;20(1):380. doi: 10.1186/s12885-020-06876-4.

  PMID: 32370765 BACKGROUND

• Olson R, Abraham H, Leclerc C, Benny A, Baker S, Matthews Q, Chng N, Bergman A, Mou B, Dunne EM, Schellenberg D, Jiang W, Chan E, Atrchian S, Lefresne S, Carolan H, Valev B, Tyldesley S, Bang A, Berrang T, Clark H, Hsu F, Louie AV, Warner A, Palma DA, Howell D, Barry A, Dawson L, Grendarova P, Walker D, Sinha R, Tsai J, Bahig H, Thibault I, Koul R, Senthi S, Phillips I, Grose D, Kelly P, Armstrong J, McDermott R, Johnstone C, Vasan S, Aherne N, Harrow S, Liu M. Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET. BMC Cancer. 2024 Feb 3;24(1):171. doi: 10.1186/s12885-024-11905-7.

  PMID: 38310262 DERIVED

Study Officials

• Robert Olson, MD, MSc, FRCPC

  BC Cancer - Prince George

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Olson, MD, MSC, FRCPC

CONTACT

250-645-7300; rolson2@bccancer.bc.ca

Jordanna Laing, MSc

CONTACT

250-645-7300; jordanna.laing@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Radiation Oncologist

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 24, 2023
• Study Start: April 16, 2025
• Primary Completion (Estimated): April 30, 2035
• Study Completion (Estimated): May 30, 2035
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

CA (6); IE (7)