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

• ClinicalTrials.gov Identifier: NCT01446744
• Recruitment Status: Active, not recruiting
• First Posted: October 5, 2011
• Last Update Posted: October 5, 2023
• Sponsor: Lawson Health Research Institute
• Collaborators: London Regional Cancer Program, Canada; VU University of Amsterdam
• Information provided by (Responsible Party): David Palma, Lawson Health Research Institute

Tracking Information

• First Submitted Date: September 29, 2011
• First Posted Date: October 5, 2011
• Last Update Posted Date: October 5, 2023
• Study Start Date: November 2011
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 3, 2011): Overall Survival [ Time Frame: At approximately end of year 4 (study completion) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 5, 2022)

• Quality of life: Assessed with the Functional Assessment of Cancer Therapy: General (FACT-G) [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Toxicity: Assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4 for each organ treated (e.g. liver, lung, bone) [ Time Frame: At approximately the end of years 1, 2, 3, and 4 (study completion) ]
• Progression-free survival [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Lesional control rate [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Number of cycles of further chemotherapy/systemic therapy [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]

Original Secondary Outcome Measures (submitted: October 3, 2011)

• Quality of life [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Toxicity [ Time Frame: Annually ]
• Progression-free survival [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Lesional control rate [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]
• Number of cycles of further chemotherapy/systemic therapy [ Time Frame: At approximately end of year 2, and end of year 4 (study completion) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Tumors (SABR-COMET)
• Official Title: Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Tumors (SABR-COMET): A Randomized Phase II Trial
• Brief Summary: Stereotactic Ablative Radiotherapy (SABR) is a new radiation treatment that delivers high-dose, precise radiation to small tumors in 1-3 weeks of treatment. This new technique can potentially allow radiation treatments to be focused more precisely, and delivered more accurately than with older treatments. This improvement could help by reducing side effects and by improving the chance of controlling the cancer by more precisely treating the cancer. The purpose of this study is to compare SABR with current approaches of chemotherapy and conventional radiotherapy to assess the impact on overall survival and quality of life.

Detailed Description

TREATMENT PLAN

6.0.1 Standard Arm (Arm 1)

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.

Treatment recommendations are as follows:

Brain: Whole brain radiotherapy i.e. 20 Gy in 5 fractions, 30 Gy in 10 fractions

Lung: Palliative radiotherapy as per 2011 consensus guidelines.15 i.e. 8 Gy in 1 fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions

Bone: Palliative radiotherapy as per 2011 consensus guidelines.16 i.e. 8 Gy in 1 fraction (most common), 20 Gy in 5 fractions, 30 Gy in 10 fractions

Liver: 20 Gy in 5 fractions if standard institutional practice

6.0.2 Treatment Planning for Standard Arm

Treatment planning is to be done using CT simulation or conventional simulation (fluoroscopy) as per individual institutional practice. Simple beam arrangements, such as parallel opposed beams, are favored wherever possible.

6.1 Experimental Arm (Arm 2)

All treatments in this study are based on current protocols in clinical use at the LRCP and VUmc for treatment of lung,17 liver,18 brain,19,20 and spinal cord21 metastases. The guiding principle for radiotherapy is to achieve disease control but to minimize any potential adverse impact on quality of life. Concurrent chemotherapy or targeted therapy at the time of radiotherapy is not permitted within the 4 weeks prior to SABR. Hormone therapy is permitted.

6.1.1 Dose/Fractionation

Lung- tumors 3 cm or less surrounded by lung parenchyma, 54(Gy) in 3 fractions

• Abutting chest wall or >3 cm, 55(Gy)in 5 fractions, every second day
• Within 2 cm of mediastinum or brachial plexus, 60(Gy),8* fractions, every second day

Bone -Any bone except femur,35(Gy), in 5 fractions,daily

• vertebral body,16-20(Gy)in 1 fraction, single dose, or 30Gy in 3 fractions, every second day

Brain - Non-radiosurgical,40(Gy) to metastases, in 5 fractions,daily

• If whole brain treated, then simultaneous boost to each lesion,20 Gy whole brain (optional), in 5 fractions, daily
• Radiosurgical, ≤1 cm, 22-24(Gy), in 1 fraction, >1 and ≤2 cm, 22-24(Gy) in 1 fraction >2 and ≤ 3 cm, 18-20(Gy) in 1 fraction Optional whole brain to follow (see text) Liver-LRCP site: Dose is based on calculated normal tissue probability of <5%,Every second day
• other sites 45-60(Gy), in 3-8 fractions, every second day

Adrenal, 60 (Gy), in 8 fractions, every second day

(If whole brain treated, then simultaneous boost to each lesion)

6.1.2 Immobilization

Treatment will be setup using reproducible positioning, verified using an on-line protocol, for all patients in this study. Immobilization may include a custom immobilization device, such as thermoplastic shell or vac-lok bag, as per individual institutional practice when delivering SABR. Some centers do not use immobilization devices and have demonstrated high degrees of accuracy; this is acceptable in this study.

6.1.3 Imaging/Localization/Registration All patients in Arm 2 will undergo planning CT simulation. 4-dimensional CT will be used for tumors in the lungs or liver. Axial CT images will be obtained throughout the region of interest. For centres using stereotactic radiosurgery platforms, real-time tumor tracking and orthogonal imaging systems are permitted.

Any center which is not yet experienced in lesions at any specific sub-site (e.g. adrenal metastases) shall be eligible to participate by including only patients with lesions at other pre-specified sites

It is strongly recommended that the doses to organs at risk are not to be exceeded - in some specific cases, this may require lower doses or higher fractionations than listed here. Such changes in dose will require approval of one of the local principal investigators. (see section 6.2)

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Tumors

Intervention

• Radiation: Stereotactic ablative radiotherapy
  Total dose and number of fractions will depend on the site of disease. Treatment will be given daily, or every other day, over 1 -3 weeks.
• Radiation: palliative radiotherapy

  Investigators should follow the principles of palliative radiotherapy as per the individual institution. Treatment recommendations are as follows:

  Brain: Whole brain radiotherapy i.e. 20 Gy in 5 fractions, 30 Gy in 10 fractions

  Lung: Palliative radiotherapy as per 2011 consensus guidelines.15 i.e. 8 Gy in 1 fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions

  Bone: Palliative radiotherapy as per 2011 consensus guidelines.16 i.e. 8 Gy in 1 fraction (most common), 20 Gy in 5 fractions, 30 Gy in 10 fractions

  Liver: 20 Gy in 5 fractions if standard institutional practice

Study Arms

• Active Comparator: Standard arm
  Standard of care, palliative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist
  Intervention: Radiation: palliative radiotherapy
• Experimental: Stereotactic arm
  Stereotactic ablative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist
  Intervention: Radiation: Stereotactic ablative radiotherapy

Publications *

• Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838. doi: 10.1200/JCO.20.00818. Epub 2020 Jun 2.
• Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Griffioen G, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Bauman GS, Warner A, Senan S. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019 May 18;393(10185):2051-2058. doi: 10.1016/S0140-6736(18)32487-5. Epub 2019 Apr 11.
• Palma DA, Haasbeek CJ, Rodrigues GB, Dahele M, Lock M, Yaremko B, Olson R, Liu M, Panarotto J, Griffioen GH, Gaede S, Slotman B, Senan S. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial. BMC Cancer. 2012 Jul 23;12:305. doi: 10.1186/1471-2407-12-305.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 3, 2011): 99
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 18 or older
• Willing to provide informed consent
• Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
• ECOG performance status 0-1

• Controlled primary tumor

  a. defined as: at least 3 months since original tumor treated definitively, with no progression at primary site

• All sites of disease can be safely treated based on criteria below
• Maximum 3 metastases in any single organ system (i.e. lung, liver, brain, bone)
• Life expectancy >6 months
• Not a candidate for surgical resection at all sites: surgery to all sites not recommended by multidisciplinary team, or unfit or declining surgery
• Prior chemotherapy allowed but no systemic therapy 4 weeks prior to first fraction of radiotherapy, during radiotherapy, or for two weeks after last fraction

• Patients with metastases that have been previously treated (e.g. prior resection, Radiofrequency Ablation (RFA) or radiotherapy):

  a. If that previously treated metastasis is controlled on imaging, the patient is eligible for this study and that site does not need treatment

  a. If that previously treated metastasis is NOT controlled on imaging:

  1. If the previous treatment was surgery, the patient is eligible if that site can be treated by SABR
  2. If the previous treatment was radiotherapy or RFA, the patient is ineligible.
• Patient presented at multidisciplinary tumor board or quality-assurance rounds.

Exclusion Criteria:

• Serious medical comorbidities precluding radiotherapy
• Bone metastasis in a femoral bone
• Patients with 1-3 brain metastasis and no disease elsewhere (these patients should not be randomized but treated with stereotactic radiotherapy as per results of randomized trials)
• Prior radiotherapy to a site requiring treatment
• Complete response to first-line chemotherapy (i.e. no measurable target for SABR)
• Malignant pleural effusion
• Inability to treat all sites of active disease
• Clinical or radiologic evidence of spinal cord compression OR tumor within 3 mm of spinal cord on Magnetic Resonance Imaging (MRI).
• Dominant brain metastasis requiring surgical decompression
• Pregnant or lactating women

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Netherlands, United Kingdom

Administrative Information

• NCT Number: NCT01446744
• Other Study ID Numbers: R-11-605; SABR-COMET ( Other Identifier: OCREB )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: David Palma, Lawson Health Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Lawson Health Research Institute
• Original Study Sponsor: David Palma

Collaborators

• London Regional Cancer Program, Canada
• VU University of Amsterdam

Investigators

• Principal Investigator: David Palma, MD, PhD; London Regional Cancer Program of the Lawson Health Research Institute
• Principal Investigator: Suresh Senan, MRCPFRCR,PhD; Amsterdam UMC, location VUmc

• PRS Account: Lawson Health Research Institute
• Verification Date: October 2023