Acronym

COLLISION RELAPSE

Name of the study

COLLISION RELAPSE Trial - Recurrent Colorectal Liver Metastases: Repeat Local Treatment +/- Neoadjuvant Systemic Therapy - a Phase III Prospective Randomized Controlled Trial

Researchers and contact information

Lead investigator

Prof. Dr. M.R. Meijerink

Dr. K.S. Versteeg

Dr. R.J. Swijnenburg

Study coordinator

Drs. M. Dijkstra, m.dijkstra3@amsterdamumc.nl

Drs. H.H. Schulz, h.h.schulz@amsterdamumc.nl

Summary study

Rationale: After initial treatment of CRLM, new intrahepatic recurrence develops in 64%-85% of patients. To treat recurrent CRLM local treatment is considered standard of care. With upfront repeat local treatment 5-year reaches 51%. Given the poorer prognosis associated with patients with recurrent disease, attributed to presumed worse tumor biology and the presence of intrahepatic micrometastases, neoadjuvant chemotherapy prior to repeat local treatment has been suggested to prolong survival and to select responders who will benefit from local treatment. Although the recommendation of neoadjuvant chemotherapy followed by repeat local treatment is frequently reported, the exact role of neoadjuvant chemotherapy prior to repeat local treatment in case of recurrent and locally treatable CRLM remains uncertain.

Primary objective: 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.

Study design: The COLLISION RELAPSE trial is a prospective multicenter phase III randomized controlled trial. The primary conducting center will be the Amsterdam UMC (Amsterdam, the Netherlands). A total number of 360 patients will be randomized (NR) into one of two arms: arm A (control group) upfront repeat local treatment (n=180) and arm B (intervention group) 12 weeks of neoadjuvant systemic therapy followed by repeat local treatment (n=180).

Primary endpoint: Primary endpoint is overall survival (OS; intention-to-treat analysis)

Secondary endpoints: Secondary endpoints are distant progression-free survival (DPFS), local tumor progression-free survival (LTPFS) per patient and per tumor treated, systemic therapy related toxicity and procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY).

Sample size: We hypothesize that neoadjuvant systemic therapy prior to repeat local treatment is superior to  direct local treatment for the selected patient groups in terms of the primary objective (overall survival). The Cox proportional hazards model (1-sided; superiority) is used for the sample size calculations. Given the PASKWIL criteria for adjuvant treatment for the benefit of OS from the Dutch Society of Medical Oncology, we consider OS improved if increased by 5% with 3-year follow up with corresponding hazard ratio (HR) of 0.7 to represent the upper limit of superiority (210). The total number of events needed to estimate the HR of 0.7 with 80% at a significance level (alpha) of 0.05 is equal to 195. Following results of the LiverMetSurvey by Viganó et al., 5-year probability of event is 55.9% (overall probability of event, pE =0.559). Therefore, the calculated raw sample size is 348 (NRS).

 

Intervention

Control arm

Repeat local treatment

 

Experimental arm

Neoadjuvant systemic therapy followed by repeat local treatment

Participating centers

Participation formally approved by EC

Noordwest Ziekenhuisgroep Alkmaar, Leids Universitair Medisch Centrum, Maxima Medisch Centrum