The primary objective is to demonstrate superiority of neoadjuvant systemic therapy followed by repeat local treatment as compared to upfront repeat local treatment in patients with at least one locally treatable recurrent CRLM in the absence of extrahepatic disease.
Age >18 years
Good performance status (ECOG 0-2 // ASA 1-3)
Histological documentation of primary colorectal tumor
Local treatment performed for initial CRLM
Extrahepatic disease
MSI/dMMR
Radical local treatment unfeasible or unsafe (e.g. insufficient future liver volume)
Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites)
Parallel
Neoadjuvant systemic therapy (CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B)
DrugStandard first line systemic treatment: CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B CAPOX 4x (12 weeks) FOLFOX/FOLFIRI 6x (12 weeks) Maximum 4 cycles of CAPOX or 6 cycles of FOLFOX/FOLFIRI +/- bevacizumab regardless of the location of primary tumor or RAS/BRAF mutation
Repeat local treatment
Other interventionChoice of repeat local treatment is to the discretion of the local investigator, and may be selected on a per patient basis. The safety, feasibility and preferred type of surgical resection(s) is at the discretion of the liver surgeon (whether or not combined with thermal ablation). The safety, feasibility and preferred type of thermal ablation(s) is at the discretion of the interventional radiologist (whether or not combined with surgical resection).
Overall survival (OS) per patient
Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date of death of the patient or to the last day of follow-up (censored).
Distant progression-free survival (DPFS) per patient
Distant progression free survival (DPFS; per patient analysis): Overall DPFS is defined as the time from randomization to the time of disease progression (according to the RECIST 1.1 guideline) or cancer related death (events), death related to other causes is considered a competing risk
Local tumor progression-free survival (LTPFS) per patient and per tumor treated
Local tumor progression free survival (LTPFS; per tumor and per patient analysis): Overall LTPFS is defined as the time from randomization to the time of local disease progression, new metastases (events), censoring the date of death from any cause (competing risk), completion ablations performed within 6 weeks for residual tumor are not considered events for the local tumor progression analysis
Systemic therapy related toxicity per patient following neoadjuvant systemic therapy
Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0
Procedural morbidity and mortality per patient following repeat local treatment
Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications
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