Chemotherapy for Resectable Colorectal Liver Metastases

Completed

• Conditions: Metastatic Colorectal Cancer; Metastatic Liver Cancer
• Interventions: Other: Liver resection and Neoadjuvant chemotherapy; Other: Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy; Other: Liver resection and Adjuvant chemotherapy; Procedure: Liver resection

• Registration Number: NCT04513457
• Lead Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Brief Summary

There is a degree of uncertainty regarding the role of perioperative chemotherapy (CTx) in the treatment of resectable colorectal liver metastases (CRLM). In the clinical practice, the combination of surgery and CTx is increasingly accepted as treatment for CRLM, especially in the context of patients with synchronous disease or metachronous disease with a high risk of recurrence. However, controversy exists whether all patients with resectable CRLM benefit from perioperative CTx.

There is paucity of good quality studies on this topic. A pooled analysis of two phase III randomized clinical trial, closed prematurely because of slow accrual, showed a marginal statistical significance in favor of adjuvant CTx. Nevertheless, long term results of the EPOC trial founded benefit in disease free survival (DFS) with no difference in overall survival (OS) when perioperative CTx with FOLFOX4 was compared with surgery alone for resectable CRLM. Furthermore, a retrospective series from Ayez et al showed that patients with a high CRS benefit from neo-adjuvant CTx while in patients with a low risk profile did not. On the other side, another retrospective series from the MSKCC showed the timing of additional CTx for resectable CRLM was not associated with improved outcomes. The ongoing CHARISMA trial is currently comparing the outcomes of neo-adjuvant CTx followed by surgery versus surgery alone in high-risk patients with resectable CRLM.

This uncertainty regarding CRLM management may partly be due to the fact that these studies are not well powered to detect minor differences in long term outcomes and they often involved a very heterogenous group of patients with both synchronous and metachronous CRLM, not stratified by clinical risk score (CRS) as described by Fong et al.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-01
• Primary Completion: 2020-07-31
• Study First Submitted: 2020-08-11
• Study First Submitted QC: 2020-08-13
• Study First Posted: 2020-08-14
• Study Completion: 2020-09-30
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-26
• Last Update Posted: 2021-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 967

Inclusion Criteria

• Patients older than 18 years with resectable liver metastases of histologically confirmed primary colorectal carcinoma.
• Minimum follow-up of five years.

Exclusion Criteria

• Patients with extrahepatic disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Liver resection and Neoadjuvant chemotherapy	Liver resection and Neoadjuvant chemotherapy	Liver resection and Neoadjuvant chemotherapy
Liver resection, Neoadjuvant and Adjuvant chemotherapy	Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy	Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy
Liver resection and Adjuvant chemotherapy	Liver resection and Adjuvant chemotherapy	Liver resection and Adjuvant chemotherapy
Liver resection	Liver resection	Liver resection

Primary Outcome Measures

Name	Time	Method
Peri-operative morbidity	5 years of follow-up	Peri-operative morbidity
Overall survival based on perioperative treatment	5 years of follow-up	Overall survival based on perioperative treatment
Disease-free survival based on perioperative treatment	5 years of follow-up	Disease-free survival based on perioperative treatment
Cancer survival based on perioperative treatment	5 years of follow-up	Cancer survival based on perioperative treatment
Peri-operative mortality	5 years of follow-up	Peri-operative mortality

Secondary Outcome Measures

Name	Time	Method
Overall survival, cancer survival and disease-free survival related with biological markers	5 years of follow-up	Overall survival, cancer survival and disease-free survival related with biological markers
Overall survival, cancer survival and disease-free survival based related with simultaneous thermal ablation performed at the same time of the surgical excision.	5 years of follow-up	Overall survival, cancer survival and disease-free survival based related with simultaneous thermal ablation performed at the same time of the surgical excision.
Overall survival, cancer survival and disease-free survival related with hidden no resected liver lesions.	5 years of follow-up	Overall survival, cancer survival and disease-free survival related with hidden no resected liver lesions.

Trial Locations

Locations (9)

Centre Hospitalier Universitaire de Reims; 🇫🇷 Reims, France

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Comunidad Valenciana, Spain

Hospital Universitario de Badajoz; 🇪🇸 Badajoz, Spain

Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario de Jaén; 🇪🇸 Jaén, Spain

Hospital Dr. Josep Trueta; 🇪🇸 Girona, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Liverpool University Hospitals NHS Foundation Trust; 🇬🇧 Liverpool, United Kingdom