Trial details

Trial short name: ULTRAS

Official title: Ultra-high dose radiation for Liver metastasis using MR-guided TReatment with stereotactic Ablative Single-fraction (ULTRAS): phase III randomized controlled trial

Principal Investigator: Dr. Sylvia Ng

Cancer type: Gastrointestinal
Cancer location: Liver
Disease stage: Advanced Cancer
Trial phase: Phase 3
Intervention: radiation

Registration #: NCT06362395

Contact e-mail: cancerclinicaltrials@sunnybrook.ca

Trial description:
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.

Key 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 • 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 single fraction SBRT with 16Gy or 24Gy, as soon as the total number of treated metastatic liver lesions with SBRT will be ≤5 • Patients must be Child-Pugh score A within one month prior to study entry • ECOG 0-2 • Suitable for MR-linac treatment Key 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) • 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)