MOR-1 Expression in Colorectal Cancer and Disease-free Survival Relationship. Five-year Follow-up. (MOROCCO)

Mu Opioid Receptor 1 Expression in Colorectal Cancer and Disease-free Survival Relationship (Morocco). Five-year Follow-up.

Colorectal cancer (CRC) is a global burden and one of the most frequent types of cancer. Colorectal cancer therapy is complex and surgery remains the cornerstone for its treatment, combined with chemotherapy and radiotherapy. At diagnosis time, stage II / III is the predominant . There is a growing interest on the potential effect of perioperative anesthetic management on cancer growth and spread. Preclinical studies suggest that opioids could promote direct tumor growth, angiogenesis, metastasis and immunosuppression of cellular and humoral responses, mainly mediated by Mu opioid receptor 1 (MOR-1) activation. Association between increased expression of MOR-1and or perioperative opioids use and shorter DFS or OS has been demonstrated in lung, prostate, gastric and esophagus cancers. Furthermore a pooled analysis suggested that methylnaltrexone, a peripherally acting Mu-opioid receptor antagonist (PAMORA) was associated with increased survival in patients with advanced cancer.

Thus, the expression of the MOR-1 is an indicator of poor prognosis in some cancer types, but its relevance in colon cancer is unknown. The hypothesis of this study is that the increased MOR-1expression in tumor samples from colorectal cancer could be associated to poor disease free survival.

These findings would be of great clinical relevance in order to avoid perioperative opioid use in oncological patients. Moreover PAMORAs could be a valuable tool in perioperative antitumor treatment, since currently these drugs are currently used with confirmed tolerability and low adverse effects in the management of opioid-induced constipation (Opioid Induced Constipation-OIC). Besides MOR 1 expression could constitute a biomarker that guide the investigators to perform neoadjuvant therapy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: ELISA for MOR-1 expression

Detailed Description

PRIMARY OBJECTIVES:

To evaluate the association between Mu opioid receptor 1 (MOR-1) expression in patients with colorectal cancer stage II / III submitted to scheduled curative surgery and disease-free survival (DFS) five years follow up after surgery.

SECONDARY OBJECTIVES:

To evaluate the association between the MOR-1 expression in patients with colorectal cancer stage II / III undergoing scheduled curative surgery and overall survival (OS) five years follow up after surgery.

To evaluate the association between MOR-1 expression in patients with colorectal cancer stage II / III submitted to scheduled curative surgery and perioperative complications until postoperative day 28th after surgery.

To evaluate the association between perioperative opioids dose (morphine equivalents) and disease-free survival/overall survival until five years after surgery.

To evaluate MOR-1 expression differences in paraffin samples from patients with colorectal cancer stage II / III submitted scheduled colorectal surgery between the tumor tissue and the adjacent nontumorous tissue.

• Study Type: Observational
• Enrollment (Actual): 174

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain
    • Hospital Universitario La Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing scheduled colorectal surgery stage II / III for primary colorectal cancer between 01/01/2010 from 31/12/2013.

Description

Inclusion Criteria:

• Patients older than 18 years.
• Colorectal scheduled surgery between January 2010- December 2013.
• Colon / rectum neoplasia Stage II / III (T3 / T4 N + M0).

Exclusion Criteria:

• Stage I or Stage IV
• Non-oncological colorectal surgery
• Non-elective surgery

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TT; Tumor Tissue. Colon or rectum neoplasia stage II and III tumor tissue.	Other: ELISA for MOR-1 expression; To evaluate MOR-1 expression differences by immunohistochemical analysis (ELISA - semiquantitative) in paraffin samples from patients with colorectal cancer stage II / III submitted scheduled colorectal surgery between the tumor tissue and the adjacent nontumorous tissue.
NTT; Nontumorous Tissue. Colon or rectum neoplasia stage II and III adjacent nontumorous tissue.	Other: ELISA for MOR-1 expression; To evaluate MOR-1 expression differences by immunohistochemical analysis (ELISA - semiquantitative) in paraffin samples from patients with colorectal cancer stage II / III submitted scheduled colorectal surgery between the tumor tissue and the adjacent nontumorous tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of MOR1.	Immunohistochemical analysis (ELISA - semiquantitative) to asses expression of MOR1 in tumor tissue and adjacent nontumorous tissue.	Six months
Disease free survival.	Disease free survival 5 years after surgery.	Five years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence.	Five years follow up after surgery.	Five years.
Lymphatic relapse.	Five years follow up after surgery.	Five years.
Metastasis.	Reproduction or extension of the tumor to another part of the body. Five years follow up after surgery.	Five years.
Type of recurrence (local, regional or distant).	Five years follow up after surgery.	Five years.
Overall Survival.	Five years follow up after surgery.	Five years.
Morphine equivalents.	Morphine equivalents consumption during perioperative period.	During surgery and up to 96 hours during the perioperative period.
Perioperative complications.	Perioperative complications until postoperative day 28th.	28 days.

Collaborators and Investigators

• Sponsor: Hospital Universitario La Fe
• Investigators: Principal Investigator: OSCAR DIAZ-CAMBRONERO, MD, Hospital Universitario La Fe

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2018
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: July 18, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: CANCER, COLON, OPIOIDS, MOR-1
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: ODC-MOR-2018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No