A Phase II Trial to Evaluate the Strategy of Integrating Local Ablative Therapy with First-Line Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer (RESOLUTE)

Local ablative therapy: a maximum of three LAT modalities can be administered for each participant, with a maximum of 2 modalities per organ, provided all LAT can be delivered within 12 weeks and participant can safely resume systemic treatment to a total of 6 months. LAT modalities allowed include surgical resection, stereotactic radiotherapy (SRT), laparoscopic or percutaneous thermal ablation [radiofrequency ablation (RFA) or microwave ablation (MWA)]. The LAT modalities will be delivered by specialists in the field (surgeons, radiation oncologists and/or interventional radiologists). The precise mode of delivery and number of times the LAT modality is delivered is case-dependent and is determined at a multi-disciplinary meeting (MDM). Standard of care first-line systemic treatment: first-line systemic treatment of 3-6 months prior to study enrolment. If after completing LAT, participant has not completed 6 months of first-line systemic treatment upfront, they may resume treatment to a total of 6 months of treatment. For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion. The treating clinician may choose to discontinue systemic treatment following LAT for patients who have experienced prior intolerable toxicity. Local guidelines will be implemented to ensure intervention fidelity. Case report forms (CRF) specific to each LAT modality will capture specific mode of delivery, organ being treated and number of times the intervention is delivered over a period of time.