Clinical trial NCT03721341: Stereotactic Ablative Radiotherapy for Comprehensive Treatment of 4-10 Oligometastatic Tumors
Official title: A Randomized Phase III Trial of Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of 4-10 Oligometastatic Tumors (SABR-COMET 10)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Tumors
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Amsterdam University Medical Centre, VUmc Site
name: British Columbia Cancer - Centre for the North
name: Beaston West of Scotland Cancer Centre
name: London Health Sciences Centre
First posted: 2018-10-26
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival at Study Completion
timeFrame: At approximately end of year 6 (study completion)
Secondary outcomes:
measure: Progression-free Survival
timeFrame: At approximately year 3, and end of year 6 (study completion)
measure: Time from randomization to development of new metastatic lesions
timeFrame: At approximately end of year 6 (study completion)
measure: Quality of Life as measured by the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire
timeFrame: At approximately end of year 6 (study completion)
measure: Quality of Life as measured by the EuroQOL Group EQ-5D-5L questionnaire
timeFrame: At approximately end of year 6 (study completion)
measure: Toxicity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
timeFrame: End of years 1, 2, 3, 4, 5, and 6 (study completion)
measure: Overall Survival at midpoint of Study
timeFrame: At approximately year 3 (midpoint)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Victoria
country: Canada
facility: BC Cancer Agency, Vancouver Island Centre
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authortiy
state: Nova Scotia
city: Kitchener
country: Canada
facility: Grand River Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program of the Lawson Health Research Institute
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners-Credit Valley Hospital
state: Ontario
city: St. Catharines
country: Canada
facility: Niagra Health System
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal-CHUM
state: Quebec
city: Amsterdam
country: Netherlands
facility: VU University Medical Centre
city: Zürich
country: Switzerland
facility: University Hospital of Zürich
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
Study officials:
affiliation: London Health Sciences Centre, Lawson Health Research Institute
name: David Palma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam University Medical Centre, VUmc Site
name: Suresh Senan, MRCP, FRCR
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Cancer - Centre for the North
name: Robert Olson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beaston West of Scotland Cancer Centre
name: Stephen Harrow, MB ChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.