Clinical trial NCT03601351: MOR-1 Expression in Colorectal Cancer and Disease-free Survival Relationship. Five-year Follow-up.
Official title: Mu Opioid Receptor 1 Expression in Colorectal Cancer and Disease-free Survival Relationship (Morocco). Five-year Follow-up.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: CANCER, COLON, OPIOIDS, MOR-1
Lead sponsor: Hospital Universitario La Fe
Sponsor class: OTHER
First posted: 2018-07-26
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Expression of MOR1.
timeFrame: Six months
measure: Disease free survival.
timeFrame: Five years.
Secondary outcomes:
measure: Local recurrence.
timeFrame: Five years.
measure: Lymphatic relapse.
timeFrame: Five years.
measure: Metastasis.
timeFrame: Five years.
measure: Type of recurrence (local, regional or distant).
timeFrame: Five years.
measure: Overall Survival.
timeFrame: Five years.
measure: Morphine equivalents.
timeFrame: During surgery and up to 96 hours during the perioperative period.
measure: Perioperative complications.
timeFrame: 28 days.
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
Study officials:
affiliation: Hospital Universitario La Fe
name: OSCAR DIAZ-CAMBRONERO, MD
role: PRINCIPAL_INVESTIGATOR
References: