Name of the study
COLLISION trial: Colorectal liver metastases: surgery versus thermal ablation – a phase III single-blind prospective randomized controlled trial
Researchers and contact information
Dr. M.R. (Martijn) Meijerink E: MR.Meijerink@vumc.nl
Other principal investigator
Dr. M. P. (Petrousjka) van den Tol E: MP.firstname.lastname@example.org
Dr. V.M.H. (Veerle) Coupé E: V.Coupe@vumc.nl
Drs. Sanne Nieuwenhuizen, PhD candidate, Study coordinator E: email@example.com
Rationale: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of this randomized controlled trial.
Primary objective: to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease.
Study design: Halfway 2017, accrual of 687 patients with at least one CRLM (≤3cm) will begin. Patients will undergo either surgical resection (control arm) or thermal ablation (experimental arm) of appointed target lesion(s) (≤3cm).
Primary endpoint: Primary endpoint is overall survival (OS; intention-to-treat analysis)
Secondary endpoints: Secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL; EORCT QLQ-C30 questionnaires), cost-effectiveness ratio (ICER; in general and per EQ-5D and PCQ questionnaires) and quality-adjusted life years (QALY).
Sample size: The Cox proportional hazards model (1-sided; non-inferiority or superiority) is used for sample size calculations. Given the superior safety profile we consider a hazard ratio of 1.3 to represent the upper limit of non-inferiority (non-inferiority margin). An HR of 1.3 corresponds to a 56.5% chance of the ablated patients to die first ((P = HR/(1 + HR) = 1.3/(1 + 1.3) = 0.565 (56.5%)). With 3 years of patient accrual and five years of follow-up we will have reached 60% of events (death) in approximately 6.5 years (overall probability of event, pE =0.6). The calculated sample size therefore is 599 (NS).To account for a 10% drop-out ratio (NDO=69) prior to randomization and a 3% loss to follow-up (NLTFU=18) after randomization we need to include 687 patients (NI)(alpha = 0.05, power of 80%). A total number of 618 patients will be randomized (NR) into one of two arms: arm A will undergo surgical resection (n=309) and arm B thermal ablation (n=309) for appointed target lesions.
Participation formally approved by EC
Antoni van Leeuwenhoek Ziekenhuis, Amsterdam Leids Universitair Medisch Centrum, Leiden Maastricht Universitair Medisch Centrum, Maastricht Radboud Universitair Medisch Centrum, Nijmegen VU Universitair Medisch Centrum, Amsterdam Ziekenhuis Gelderse Vallei, Ede
Participation not yet formally approved by EC
Academisch Medisch Centrum Amsterdam, Amsterdam Medisch Centrum Leeuwarden, Leeuwarden Onze Lieve Vrouwe Gasthuis, Amsterdam