Timisnar - Biomarkers Substudy (Timisnar-mirna) (TiMiSNAR-miRNA)

April 15, 2024 updated by: Igor Monsellato, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Timing To Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy For Rectal Cancer: A Multicenter Randomized Controlled Trial - Biomarkers SubStudy

Neoadjuvant chemoradiotherapy (nCHT) followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage in the primary tumor and lymph nodes (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading (TRG) and lymph node status (ypN) helped to visualize individual tumor sensitivity to CRT retrospectively. Since the response to nCHT is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed.

As a potential alternative to CEA and ctDNA, microRNAs (miRNAs) are currently under investigation to serve as blood-based biomarkers. miRNAs are small, noncoding RNAs that regulate gene expression by post-transcriptional mRNA binding, which promotes the destabilization of target miRNAs. The target specificity of miRNAs is largely predetermined by their so-called "seed-sequence" (containing nucleotides at position 2-7 of the miRNA). They are highly conserved between species, stable and easy detectable even in small concentrations. They have been widely analyzed in physiological and pathological processes, and their expression is tissue specific.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Neoadjuvant chemoradiotherapy (nCHT) followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage in the primary tumor and lymph nodes (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading (TRG) and lymph node status (ypN) helped to visualize individual tumor sensitivity to CRT retrospectively. Since the response to nCHT is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed.

Blood samples, i.e. Liquid Biopsy, however, offer several advantages:

  1. Taking blood samples is less invasive, less expensive, easy to schedule, and nearly without any severe complications.
  2. Blood samples are a source of fresh DNA and RNA, without modifications due to preservatives; especially in the case of rectal cancer, beyond intratumoral heterogeneity, tumor biopsies are in general accompanied by normal, adenomatous or stromal tissue. This contamination may affect results of molecular analyses
  3. Investigating blood from patients can account for molecular heterogeneity and surrogate for tumor burden since tumor-derived fragments or biomarkers are collected from all tumor cells in a patients' body through circulation.
  4. Liquid biopsy may offer both the possibility of dynamic monitoring under treatment and the possibility to assess disease activity even after pathologic complete response (pCR) or after resection of the tumor when no tissue is left for molecular analyses.

In clinical routines, to date, carcinoembryonic antigen (CEA) is established as a colorectal cancer (CRC) related tumor marker but is not recommended as a screening test for colorectal cancer. First, normal levels of CEA do not exclude the possibility of a colorectal cancer. Second, an elevated CEA is not categorically associated with CRC, or in the period of follow-up with disease progression. Circulating tumor DNA (ctDNA) represents nowadays, the main approach to monitor tumor burden and therapy resistance, to evaluate the presence of residual disease after potentially curative treatment and to monitor disease recurrence with high sensitivity and specificity.

As a potential alternative to CEA and ctDNA, microRNAs (miRNAs) are currently under investigation to serve as blood-based biomarkers. miRNAs are small, noncoding RNAs that regulate gene expression by post-transcriptional mRNA binding, which promotes the destabilization of target miRNAs. The target specificity of miRNAs is largely predetermined by their so-called "seed-sequence" (containing nucleotides at position 2-7 of the miRNA). They are highly conserved between species, stable and easy detectable even in small concentrations. They have been widely analyzed in physiological and pathological processes, and their expression is tissue specific.

To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Alessandria, Italy
        • Recruiting
        • SS. Antonio e Biagio e Cesare Arrigo
        • Contact:
        • Principal Investigator:
          • Igor Monsellato, PhD
        • Sub-Investigator:
          • Sara Orecchia, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All included patients in the TiMiSNAR Trial (already approved by local Ethical Committees on 8/5/2018 - NCT3465982) are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery and after adjuvant chemotherapy whenever indicated.

Description

Inclusion Criteria:

  • Age >18 years
  • cT3/4N0/+M0 confirmed on CT-scan, MRI (stratification for T3a-b-c-d)
  • Histologically-proven adenocarcinoma of the rectum
  • Eligible for a resective surgery with TME
  • Eligible for chemoradiation treatment

Exclusion Criteria:

  • Metastatic disease
  • Squamous carcinoma of the anal canal
  • Unable to complete neoadjuvant treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in expression levels of plasma miRNA
Time Frame: 5 years
the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pCR
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
miRNA expression and surgery
Time Frame: 5 years
changes in expression levels of miRNA following complete surgical resection with disease-free survival
5 years
miRNA expression and surveillance
Time Frame: 5 years
the relation between changes in miRNA during surveillance and tumor relapse
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2019

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

May 21, 2019

First Submitted That Met QC Criteria

May 22, 2019

First Posted (Actual)

May 23, 2019

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rectal Cancer

Clinical Trials on miRNA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe