The Role of Tumor-associated Macrophages in Colorectal Liver Metastases

• ClinicalTrials.gov Identifier: NCT03888638
• Recruitment Status: Completed
• First Posted: March 25, 2019
• Last Update Posted: March 25, 2019
• Sponsor: Humanitas Clinical and Research Center
• Information provided by (Responsible Party): Matteo Donadon, Humanitas Clinical and Research Center

Study Description

Brief Summary:

Colorectal cancer is a major cause of mortality worldwide. Most patients develop colorectal liver metastases (CLM), and for such patients hepatectomy combined with chemotherapy may be curative. Nevertheless, in the era of precision medicine there is a critical need of prognostic markers to cope with the heterogeneity of CLM patients. Tumor-associated macrophages (TAMs) pave the way to tissue invasion and intravasation providing a nurturing microenvironment formetastases. The quantification of immune landscape of tumors has provided novel prognostic indicators of cancer progression, and the quantification of TAMs might explain the heterogeneity of CLM patients. Here, we will investigate the development of a new diagnostic tool based on TAMs with the aim to define the causative role of TAMs in CLM patients. This will open new clinical scenarios both for the diagnosis, therapy and prognosis, leading to the refinement of the therapeutic output in a personalized medicine perspective.

Condition or disease	Intervention/treatment
Colorectal Liver Metastases; Colorectal Cancer; Liver Metastases; Immunotherapy	Procedure: Hepatectomy

Detailed Description:

Some preliminary data produced by the research team from Humanitas Clinical and Research Center in Milan (ITALY) have shown that TAMs in CLM are heterogeneous and that their diversity can be distinguished based on their morphology and functionality. Therefore, TAMs may represent an additional tool in the definition of the biology and prognosis of CLM patients. This preliminary finding provides us with the rationale to undertake a prospective study on a large series of CLM patients surgically resected by our unit aimed at validating the promisingcorrelation between different TAMs phenotypes and patients prognosis. The characterization of the diversity of TAMs in CLM will be refined using state of the art technology, including multi-parametric flow cytometry, single cell RNA sequencing (scRNA-seq) transcriptional profiling, metabolomic, and proteomic analyses. The expected findings will allow us to develop a new diagnostic tool based on TAMs features, which will open the way to new criteria for patient stratification and for the design of new targeted therapies in a personalized medicine perspective.

Study Design

• Study Type: Observational
• Actual Enrollment: 101 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Search for the Clinical Significance of Tumor-associated Macrophages in Patients With Colorectal Liver Metastases
• Actual Study Start Date: January 1, 2015
• Actual Primary Completion Date: December 31, 2017
• Actual Study Completion Date: March 1, 2019

Groups and Cohorts

Intervention Details:

• Procedure: Hepatectomy
  Removal of a part of the liver because of tumor
  Other Name: Liver resection

Outcome Measures

Primary Outcome Measures :

1. Survival [ Time Frame: From date of surgery until the date of first documented progression or date of death from any cause, which ever came first assessed up to 72 months] ]
   Analysis of survival after hepatic resection for colorectal liver metastases according with the tumor-associated macrophages characteristics

Biospecimen Retention:   Samples With DNA

Specimens from liver resection

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients affected by colorectal liver metastases treated by hepatectomy.

Criteria

Inclusion Criteria:

• Patients with colorectal liver metastases undergoing hepatectomy
• Full clinical, surgical, pathological and follow-up data
• Availability of tissues for the analysis

Exclusion Criteria:

• Missing (any) data
• Combination of radiofrequency or microwave ablation plus surgery

Contacts and Locations

Sponsors and Collaborators

Humanitas Clinical and Research Center

Investigators

• Principal Investigator: Matteo Donadon, MD, PhD; Humanitas University

More Information

• Responsible Party: Matteo Donadon, Assistant Professor of Surgery, Humanitas Clinical and Research Center
• ClinicalTrials.gov Identifier: NCT03888638
• Other Study ID Numbers: TAMs in CLM
• First Posted: March 25, 2019
• Last Update Posted: March 25, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplasms, Second Primary; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Liver Diseases