Predictive Value of DNA Mismatch Repair System in Colorectal Cancers (DNAMMR)

May 22, 2023 updated by: Gennaro Galizia, University of Campania "Luigi Vanvitelli"

Assessment of the DNA Mismatch Repair System is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: a Propensity Score-matched and Win Ratio Analysis

  • Microsatellite instable (MSI) tumors represent almost the 15% of all sporadic colorectal cancers (CRCs).
  • Literature data show that this unique tumor population appears to be poorly responsive to conventional chemotherapy and conversely reveals excellent results to immunotherapy.
  • Our data, as demonstrated by propensity score-matched and win ratio analysis, show that there are no substantial differences between MSI and MSS tumors in early CRC stages treated with surgery alone.
  • On the contrary, stable tumors (MSS) did much better than MSI tumors in advanced CRC stages undergoing conventional adjuvant treatment.
  • Determination of status of DNA mismatch repair system is crucial in high-risk CRCs to optimize treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Colorectal cancers (CRCs) with deficient DNA mismatch repair (MMR) system (so called dMMR or MSI tumors) represent a no-negligible part of sporadic CRCs. Prognostic value of this unique cell population remains controversial, but undoubtedly these tumors are characterized by poor response to conventional chemotherapy, an high tumor mutational burden resulting in a brisk immuno response, and, as recently observed, excellent results to the immunotherapy. The aim of this study was to evaluate, by using sophisticated statistical analyses, the predictive value of MSI status and its optimal treatment.

A series of 403 consecutive CRC patients treated by the same oncological team from 2014 to 2021 entered the study. No patients underwent immunotherapy. Immunohistochemistry, integrated by polymerase chain reaction if appropriate, was used to categorize specimens in microsatellite stable (MSS) and instable (MSI) tumors. The win ratio (WR) approach was utilized to compare composite outcomes of MSS and MSI tumors while controlling for radical versus no radical resection, propensity score-matched analysis, and reversing primary endpoint.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
403

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

CRC patients undergoing surgery

Description

Inclusion Criteria:

  • all consecutive CRC patients observed from January 2014 to December 2021

Exclusion Criteria:

  • Patients with suspected or confirmed Lynch's syndrome (12 patients) and rectal cancers (98 patients) undergoing 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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
group 1 or MSS
colorectal cancers (CRCs) with stable microsatellite
Procedure: colorectal resection
potential resective surgery
group 2 or MSI
colorectal cancers (CRCs) with unstable microsatellite
Procedure: colorectal resection
potential resective surgery

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
survival rate
Time Frame: "From date of surgical operation until the date of death from any cause assessed up to 60 months"
overall survival
"From date of surgical operation until the date of death from any cause assessed up to 60 months"

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
recurrence rate
Time Frame: "From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"
disease-free survival
"From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Campania "Luigi Vanvitelli"

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Gennaro Galizia, MD, University of Campania 'Luigi Vanvitelli'

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 4, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 24, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Università Vanvitelli Napoli

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data will be made available by contacting the principal investigator

IPD Sharing Time Frame

data will become available after conclusion of the trial and publication of the results. After that data will be available for two years.

IPD Sharing Access Criteria

gennaro.galizia@unicampania.it

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.

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