Liver MetastasesPhase 3ULTRASNCT06362395
Ultra-high Dose Radiation for Liver Metastasis Using MR-guided TReatment With Stereotactic Ablative Single-fraction
A Phase 3 study testing Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT) in people with Liver Metastases, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This international multi-centre phase 3 randomized control trial investigates whether giving a very high dose of radiation in a single treatment session (ultra-high dose: experimental) using advanced technology called MR-Linac is more effective than a high dose (control) for treating liver tumors that have spread from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases
- What is being tested?
- Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteCanada
- Study dates
- 5 Dec 2024to Sep 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed malignancy (colorectal adenocarcinoma, pancreatic adenocarcinoma, head and neck SCC, cervix SCC, skin SCC and NSCLC) with metastatic liver disease detected on imaging. Biopsy of metastasis is preferred, but not mandatory.
- One, two or three liver metastases "target lesion", ≥ 2 cm from luminal and biliary structures
- Target lesions(s) that can receive high/ultra-high dose SBRT: Maximum number: 3, Maximum diameter of each target lesion: 6cm
- Non-target lesion(s) can be treated with 3- or 5-fraction SBRT for non-target liver metastases
- Patients must be Child-Pugh score A within one month prior to study entry.
- Must be ≥ 18 years of age.
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- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Expected life expectancy > 6 months.
- Suitable for MR-linac treatment (e.g., ability to lie on the treatment couch for at least one hour)
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in English. The baseline assessment must be completed within required timelines, prior to treatment start. Inability (lack of comprehension in English, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study.
- Women of child bearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after the last day of RT. Sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after SBRT.
- Women must not be pregnant or breast-feeding. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 4 weeks prior to registration. All breastfeeding women should discontinue breastfeeding prior to study registration.
Who cannot join
- Liver metastases from primary cancer other than listed in the eligibility criteria (i.e., tumor with low α/β ratio).
- Target lesion "planned for high/ultra-high dose SBRT" in proximity (<2cm) to luminal or biliary structures.
- Evidence of > 5 liver metastases (exception is in cases of oligoprogression, patients may have more than 5 liver metastases, but SBRT for target lesions will be required for 1, 2, or 3 liver metastases only).
- Any previous RT to the abdomino-pelvic region that would result in significant overlap of RT volume for the current study.
- Previous liver-directed transarterial radioembolization (note that previous transarterial chemoembolization, microwave ablation, or radiofrequency ablation are permitted).
- Individuals with severe, active co-morbidity including any of the following:
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- Chronic obstructive pulmonary disease or other pulmonary illness requiring hospitalization within 30 days of study registration
- Unstable angina and/or congestive heart failure requiring hospitalization within the 30 days of study registration
- Acute myocardial infarction within 30 days of study registration
- Diseases precluding RT (e.g., active scleroderma, lupus or inflammatory bowel disease)
- Contraindications to MR imaging (e.g. implanted metallic prostheses, defibrillators, stimulators, pacemakers, or neurotransmitters) per institutional policy on management of patients with internal and external medical devices.
- History of claustrophobia
- The total length of treatment volume is beyond the capacity of MRL machine
- Participants must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with SBRT (≥1 week break of systemic therapy prior to SBRT is required).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
This international multi-centre phase 3 randomized control trial investigates whether giving a very high dose of radiation in a single treatment session (ultra-high dose: experimental) using advanced technology called MR-Linac is more effective than a high dose (control) for treating liver tumors that have spread from other parts of the body (liver metastases). This study also aims to identify predictors of treatment response and side effects by analyzing various factors such as imaging markers and genetic profiles.
Liver metastases are common in several cancers, but surgery is often not feasible for many patients. Stereotactic body radiotherapy (SBRT), which delivers focused radiation to tumors, is an alternative treatment option. Previous studies have shown promising results with SBRT, but the optimal radiation dose for liver metastases is still uncertain.
Read more
This study will look at patients with specific types of primary cancers known to respond well to SBRT. Treatment effectiveness will be assessed by monitoring tumor control, overall survival, and quality of life.
By comparing ultra-high dose SBRT with standard high dose, the study aims to determine if the former can provide better tumor control with fewer side effects. If successful, this approach could offer a significant advancement in the treatment of liver metastases, potentially improving outcomes and quality of life for patients.
- Conditions
- Liver Metastases
- Being tested
- Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)Radiation
Precise radiation therapy delivered in a single session using magnetic resonance imaging for guidance.
| Study group | Role | What they receive |
|---|---|---|
| MRL adaptive high dose | Experimental | Magnetic resonance (MR)-guided stereotactic ablative single-fraction with high dose radiation (27Gy) Receives: Radiation: Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT) |
| MRL adaptive ultra-high dose | Other | Magnetic resonance (MR)-guided stereotactic ablative single-fraction with ultra-high dose radiation (38Gy) Receives: Radiation: Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local control (LC) of treated target lesion compared to high dose MR-guided stereotactic single-fraction radiation.
The primary endpoint is LC defined as time from randomization to local failure of the treated target lesion. The LC will be estimated by cumulative incidence function with death and/or progression outside the treated target lesion (without local failure) as competing risk factors.
Measured: 5 years
Secondary outcomes (8)
Overall survival (OS)
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Measured: 5 years
Progression free survival (PFS)
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Measured: 5 years
Intra-hepatic progression
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Measured: 5 years
Widespread progression.
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Measured: 5 years
Physician-assessed toxicities: National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) V.5.
Acute and late toxicities of treatment will be evaluated by CTCAE V5.0. The cumulative proportions of patients with at least one moderate to severe (grade 3-5) acute or late RT-related toxicity, measured by CTCAE (v5.0), will be compared between arms.
Measured: 5 years
Patients-reported toxicity: Patient Reported Outcomes - Common Terminology Criteria of Adverse Events (PRO CTCAE) V.1.
Acute and late toxicities of treatment will be evaluated by PRO CTCAE (v1.0). The cumulative proportions of patients with at least one moderate to severe (grade 3-5) acute or late RT-related toxicity, measured by PRO CTCAE (v1.0), will be compared between arms.
Measured: 5 years
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL)
Acute and late toxicities of treatment will be evaluated by QOL (for English-speaking eligible patients) will be measured using the EORTC QLQ-C15-PAL, which will be administered before and after treatment. Scores of all domains of the EORTC questionnaires for each treatment arm will be evaluated before and after treatment.
Measured: Prior to treatment and after treatment up to 5 years.
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, liver metastases (EORTC QOQ-LM21).
Acute and late toxicities of treatment will be evaluated by QOL (for English-speaking eligible patients) will be measured using the EORTC QOQ-LM21, which will be administered before and after treatment. Scores of all domains of the EORTC questionnaires for each treatment arm will be evaluated before and after treatment.
Measured: Prior to treatment and after treatment up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2024
- Study start5 Dec 2024
- Primary completionSep 2031 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06362395
- Sponsor's protocol ID
- 24-5022
- Acronym
- ULTRAS
- Status last verified
- Mar 2026
- First submitted
- 26 Feb 2024
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wong H, Ng SSW, Mohamad I, Alborz J, Stanescu T, Liu ZA, De Leon J, Tan H, Ng SP, Radhakrishna G, Bahij R, Intven M, Kirichenko A, Mesci A, Yan M, Dawson L, Augilera T, Hosni A. Ultra-high dose radiation for Liver metastasis using MR-guided TReatment with stereotactic Ablative Single-fraction (ULTRAS): study protocol for a phase III randomized controlled trial. Contemp Clin Trials. 2026 Aug;167:108381. doi: 10.1016/j.cct.2026.108381. Epub 2026 Jun 17.
PubMed 42309387
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultra-high Dose Radiation for Liver Metastasis Using MR-guided TReatment With Stereotactic Ablative Single-fraction
- ClinicalTrials.gov ID
- NCT06362395
- Acronym / sponsor ID
- ULTRAS / 24-5022
- Conditions
- Liver Metastases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 5 Dec 2024 (actual)
- Primary completion
- Sep 2031 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 12 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This international multi-centre phase 3 randomized control trial investigates whether giving a very high dose of radiation in a single treatment session (ultra-high dose: experimental) using advanced technology called MR-Linac is more effective than a high dose (control) for treating liver tumors that have spread from other parts of the body (liver metastases). This study also aims to identify predictors of treatment response and side effects by analyzing various factors such as imaging markers and genetic profiles.
Liver metastases are common in several cancers, but surgery is often not feasible for many patients. Stereotactic body radiotherapy (SBRT), which delivers focused radiation to tumors, is an alternative treatment option. Previous studies have shown promising results with SBRT, but the optimal radiation dose for liver metastases is still uncertain.
This study will look at patients with specific types of primary cancers known to respond well to SBRT. Treatment effectiveness will be assessed by monitoring tumor control, overall survival, and quality of life.
By comparing ultra-high dose SBRT with standard high dose, the study aims to determine if the former can provide better tumor control with fewer side effects. If successful, this approach could offer a significant advancement in the treatment of liver metastases, potentially improving outcomes and quality of life for patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MRL adaptive high dose | Experimental | Radiation: Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)Magnetic resonance (MR)-guided stereotactic ablative single-fraction with high dose radiation (27Gy) |
| MRL adaptive ultra-high dose | Other | Radiation: Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)Magnetic resonance (MR)-guided stereotactic ablative single-fraction with ultra-high dose radiation (38Gy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed malignancy (colorectal adenocarcinoma, pancreatic adenocarcinoma, head and neck SCC, cervix SCC, skin SCC and NSCLC) with metastatic liver disease detected on imaging. Biopsy of metastasis is preferred, but not mandatory.
- One, two or three liver metastases "target lesion", ≥ 2 cm from luminal and biliary structures
- Target lesions(s) that can receive high/ultra-high dose SBRT: Maximum number: 3, Maximum diameter of each target lesion: 6cm
- Non-target lesion(s) can be treated with 3- or 5-fraction SBRT for non-target liver metastases
- Patients must be Child-Pugh score A within one month prior to study entry.
Key exclusion criteria (14 listed)
- Liver metastases from primary cancer other than listed in the eligibility criteria (i.e., tumor with low α/β ratio).
- Target lesion "planned for high/ultra-high dose SBRT" in proximity (<2cm) to luminal or biliary structures.
- Evidence of > 5 liver metastases (exception is in cases of oligoprogression, patients may have more than 5 liver metastases, but SBRT for target lesions will be required for 1, 2, or 3 liver metastases only).
- Any previous RT to the abdomino-pelvic region that would result in significant overlap of RT volume for the current study.
- Previous liver-directed transarterial radioembolization (note that previous transarterial chemoembolization, microwave ablation, or radiofrequency ablation are permitted).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT)Precise radiation therapy delivered in a single session using magnetic resonance imaging for guidance. | Radiation | MRL adaptive high dose, MRL adaptive ultra-high dose |
Primary outcome
Local control (LC) of treated target lesion compared to high dose MR-guided stereotactic single-fraction radiation.
Time frame: 5 years
The primary endpoint is LC defined as time from randomization to local failure of the treated target lesion. The LC will be estimated by cumulative incidence function with death and/or progression outside the treated target lesion (without local failure) as competing risk factors.
8 secondary outcomes
Overall survival (OS)
Time frame: 5 years
Progression free survival (PFS)
Time frame: 5 years
Intra-hepatic progression
Time frame: 5 years
Widespread progression.
Time frame: 5 years
Physician-assessed toxicities: National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) V.5.
Time frame: 5 years
Patients-reported toxicity: Patient Reported Outcomes - Common Terminology Criteria of Adverse Events (PRO CTCAE) V.1.
Time frame: 5 years
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL)
Time frame: Prior to treatment and after treatment up to 5 years.
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, liver metastases (EORTC QOQ-LM21).
Time frame: Prior to treatment and after treatment up to 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Derived from this study: PubMed 42309387Wong H, Ng SSW, Mohamad I, Alborz J, Stanescu T, Liu ZA, De Leon J, Tan H, Ng SP, Radhakrishna G, Bahij R, Intven M, Kirichenko A, Mesci A, Yan M, Dawson L, Augilera T, Hosni A. Ultra-high dose radiation for Liver metastasis using MR-guided TReatment with stereotactic Ablative Single-fraction (ULTRAS): study protocol for a phase III randomized controlled trial. Contemp Clin Trials. 2026 Aug;167:108381. doi: 10.1016/j.cct.2026.108381. Epub 2026 Jun 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Magnetic resonance (MR)-guided stereotactic ablative single-fraction (SBRT) in people with Liver Metastases, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ali Hosni, MD (416-946-2360, ali.hosni.abdalaty@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local control (LC) of treated target lesion compared to high dose MR-guided stereotactic single-fraction radiation. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06362395, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.