Ultra-high dose MR-guided single-session radiation for liver metastases

Ultra-high Dose Radiation for Liver Metastasis Using MR-guided TReatment With Stereotactic Ablative Single-fraction

This trial will test whether one very high‑dose MR‑guided radiation session works better than a high‑dose approach for adults with up to three liver metastases.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 114 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06362395 on ClinicalTrials.gov

What this trial studies

This is an international, randomized phase 3 trial comparing a single ultra‑high dose of MR‑guided stereotactic ablative radiotherapy (single‑fraction) against a high‑dose control approach for liver metastases. Participants with up to three target liver lesions (each ≤6 cm and at least 2 cm from luminal or biliary structures) will be randomized to one of the two MR‑Linac treatment strategies. The trial collects imaging markers and genetic profiles to identify predictors of tumor response and side effects, and will track local control, toxicity, and survival outcomes. Non‑target liver lesions may be treated with multi‑fraction SBRT per protocol and all treatments are delivered on MR‑Linac systems.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed primary cancers listed in the protocol and 1–3 liver metastases each ≤6 cm, Child‑Pugh A liver function, ECOG 0–2, expected survival >6 months, and able to undergo MR‑Linac treatment are ideal candidates.

Not a fit: Patients with poor liver function (Child‑Pugh B/C), more than three liver metastases, lesions too close (<2 cm) to luminal or biliary structures, widespread uncontrolled disease, or inability to tolerate MR‑Linac are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer a one‑visit, highly focused radiation option that improves local tumor control while reducing overall treatment time.

How similar studies have performed: Previous SBRT research has shown promising local control for liver metastases, but single‑fraction ultra‑high‑dose MR‑guided treatment is relatively new and lacks large randomized phase 3 confirmation.

Eligibility criteria

Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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:
* 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).

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Ali Hosni, MD

Conditions Liver Metastases