Stereotactic Ablative Radiotherapy for Comprehensive Treatment of 4-10 Oligometastatic Tumors (SABR-COMET 10)

A Randomized Phase III Trial of Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of 4-10 Oligometastatic Tumors (SABR-COMET 10)

In patients with a limited oligometastatic burden (cancer has spread but is not yet considered metastatic), emerging evidence suggests that treatment of all sites of disease with ablative therapies can improve patient outcomes, including overall- and progression-free survival. The application of Stereotactic Ablative Radiotherapy (SABR) for patients with 4-10 metastatic deposits appears promising, yet it is unclear if all patients with greater than 3 oligometastatic lesions benefit from ablative therapies in terms of improved Overall Survival (OS), Progression Free Survival (PFS), or quality of life. The purpose of this study is to assess the impact of SABR, compared to standard of care treatment, on overall survival, oncologic outcomes, and quality of life in patients with a controlled primary tumor and 4-10 metastatic lesions.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Tumors
• Intervention / Treatment: Radiation: Palliative Radiation; Drug: Chemotherapy; Drug: Immunotherapy; Drug: Hormones; Other: Observation; Radiation: Stereotactic Ablative Radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Alfred Health
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4X1
      • BC Cancer Agency, Vancouver Island Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 0H6
      • Nova Scotia Health Authortiy
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Hospital
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program of the Lawson Health Research Institute
    • Mississauga, Ontario, Canada, L5M 2N1
      • Trillium Health Partners-Credit Valley Hospital
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Niagra Health System
    • Sudbury, Ontario, Canada, P3E 5J1
      • Health Sciences North
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H2X 0C1
      • Centre Hospitalier de l'Université de Montréal-CHUM
• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Centre
• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital of Zürich
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 or older
• Willing to provide informed consent
• Karnofsky performance score greater than 60
• Life expectancy greater than 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
• Total number of metastases 4-10
• All sites of disease can be safely treated based on a pre-plan

Exclusion Criteria:

• 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.
• For patients with liver metastases, moderate/severe liver dysfunction (Child Pugh B or C)
• 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, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases must be discussed with one of the study PIs.
• Malignant pleural effusion
• Inability to treat all sites of disease
• Any single metastasis greater than 5 cm in size.
• Any brain metastasis greater than 3 cm in size or a total volume of brain metastases greater than 30 cc.
• Metastasis in the brainstem
• Clinical or radiologic evidence of spinal cord compression
• Dominant brain metastasis requiring surgical decompression
• Metastatic disease that invades any of the following: GI tract (including esophagus, stomach, small or large bowel), mesenteric lymph nodes, or skin
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard arm; Standard of care treatment: palliative radiotherapy, chemotherapy, immunotherapy, hormones, or observation, is at the discretion of the treating oncologist.	Radiation: Palliative Radiation; Investigators should follow the principles of palliative radiotherapy as per the individual institution in order to alleviate symptoms or prevent complications. If radiotherapy is indicated, recommended doses are 8 Gy in 1 fraction, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.; Other Names: Palliative Radiotherapy; Drug: Chemotherapy; Chemotherapy may be given as indicated.; Drug: Immunotherapy; Immunotherapy may be given as indicated.; Drug: Hormones; Hormones may be given as indicated.; Other: Observation; Observation only is acceptable if this is the standard practice.
Experimental: Stereotactic Arm; Stereotactic ablative radiotherapy, plus standard of care treatment: chemotherapy, immunotherapy, hormones, or observation given at the discretion of the treating oncologist.	Drug: Chemotherapy; Chemotherapy may be given as indicated.; Drug: Immunotherapy; Immunotherapy may be given as indicated.; Drug: Hormones; Hormones may be given as indicated.; Other: Observation; Observation only is acceptable if this is the standard practice.; Radiation: Stereotactic Ablative Radiotherapy; Total dose of radiation and number of fractions will depend on the site of disease. Doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions (every 2 days), or 35 Gy in 5 fractions (daily).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at Study Completion	Time from randomization to death from any cause.	At approximately end of year 6 (study completion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Time from randomization to disease progression at any site or death.	At approximately year 3, and end of year 6 (study completion)
Time from randomization to development of new metastatic lesions	New metastatic lesions will be detected using computed tomography, magnetic resonance imaging, and/or bone scans.	At approximately end of year 6 (study completion)
Quality of Life as measured by the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire		At approximately end of year 6 (study completion)
Quality of Life as measured by the EuroQOL Group EQ-5D-5L questionnaire		At approximately end of year 6 (study completion)
Toxicity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		End of years 1, 2, 3, 4, 5, and 6 (study completion)
Overall Survival at midpoint of Study		At approximately year 3 (midpoint)

Collaborators and Investigators

• Sponsor: David Palma
• Collaborators: London Health Sciences Centre; Amsterdam University Medical Centre, VUmc Site; British Columbia Cancer - Centre for the North; Beaston West of Scotland Cancer Centre
• Investigators: Principal Investigator: David Palma, MD, London Health Sciences Centre, Lawson Health Research Institute; Principal Investigator: Suresh Senan, MRCP, FRCR, Amsterdam University Medical Centre, VUmc Site; Principal Investigator: Robert Olson, MD, British Columbia Cancer - Centre for the North; Principal Investigator: Stephen Harrow, MB ChB, Beaston West of Scotland Cancer Centre

Publications and helpful links

General Publications

• Mattes MD, Eubank TD, Almubarak M, Wen S, Marano GD, Jacobson GM, Ma PC. A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer. Clin Lung Cancer. 2021 Jul;22(4):268-273. doi: 10.1016/j.cllc.2021.01.012. Epub 2021 Jan 25.
• Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, Rodrigues GB, Lock M, Yaremko BP, Bauman GS, Ahmad B, Schellenberg D, Liu M, Gaede S, Laba J, Mulroy L, Senthi S, Louie AV, Swaminath A, Chalmers A, Warner A, Slotman BJ, de Gruijl TD, Allan A, Senan S. Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019 Aug 19;19(1):816. doi: 10.1186/s12885-019-5977-6.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2019
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: SABR-COMET 10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No