C677T and A1298C MTHFR Polymorphisms and Fluoropyrimidine Effectiveness in Metastatic Colon Cancer

March 25, 2020 updated by: Allan Ramos-Esquivel, Universidad de Costa Rica

Association of the C677T and A1298C MTHFR Polymorphisms With Chemotherapy Effectiveness Among Patients With Metastatic Colorectal Cancer

Fluoropyrimidines are the backbone of chemotherapy regimes used to treat metastatic colorectal cancer (CRC). These drugs act in different pathways of folate metabolism altering DNA synthesis mainly by inhibition of the tymidylate synthase. For this reaction the 5,10-methylenetetrahydrofolate acts as cofactor. It has been demonstrated that A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene result in reduced enzyme activity that leads to reduced availability of this important cofactor. Hence, we hypothesized that the presence of these polymorphisms are related to the efficacy and toxicity of fluoropyrimidines in patients with CRC.

Study Overview

Status

Unknown

Conditions

Detailed Description

Patients with metastatic colorectal cancer are invited to join this study at the start of treatment with any fluoropyrimidine used alone or in combination with oxaliplatin and/or irinotecan +/- bevacizumab, panitumumab or cetuximab. DNA extraction will be done from blood and tissue samples to determine the C677T (rs1801133) and 1298 A>C (rs18011131) polymorphisms of the MTHFR gene.

The patient will be followed at least for one year during treatment to determine any toxicity related to the therapy and to determine the overall survival, progression-free survival and response rate. Patients will be categorized into different categories according to the genetic status of each polymorphism.

Study Type

Observational

Enrollment (Anticipated)

65

Contacts and Locations

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

Study Locations

  • Costa Rica
      • San José, Costa Rica, 1000
        • Hospital San Juan de Dios

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

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

50 patients with metastatic colorectal cancer treated with any fluoropyrimidine.

Description

Inclusion Criteria:

  • Patients with metastatic colorectal cancer receiving first line therapy with any fluoropyrimidine (capecitabine or 5-Fluorouracil) alone or in association with oxaliplatin, and/or irinotecan, plus either bevacizumab or cetuximab/panitumumab.

Exclusion Criteria:

  • Any other malignant condition

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
Assessment of C677T and A1298C MTHFR polymorphisms and overall survival
Time Frame: From the start date of treatment until the date of death from any cause, assessed up to 24 months
Overall survival
From the start date of treatment until the date of death from any cause, assessed up to 24 months
Assessment of C677T and A1298C MTHFR polymorphisms and progression-free survival
Time Frame: From the start date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-Free survival
From the start date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Assessment of C677T and A1298C MTHFR polymorphisms and response rate
Time Frame: From the start date of treatment until the first radiological or clinical assessment, up to 6 months.
Response rate
From the start date of treatment until the first radiological or clinical assessment, up to 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of C677T and A1298 MTHFR polymorphisms and toxicity
Time Frame: From treatment initiation to detected toxicity during treatment with any fluoropyrimidine alone or in combination with oxaliplatin, irinotecan or any biological treatment as first line therapy of colorectal metastatic cancer (up to 24 months)
Prospective assessment of toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) 4.0 criteria according to the C677T and A1298C polymorphisms
From treatment initiation to detected toxicity during treatment with any fluoropyrimidine alone or in combination with oxaliplatin, irinotecan or any biological treatment as first line therapy of colorectal metastatic cancer (up to 24 months)

Collaborators and Investigators

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

Sponsor

Universidad de Costa Rica

Collaborators

Universitat Autonoma de Barcelona

Investigators

  • Principal Investigator: Allan Ramos-Esquivel, Mic, Universidad de Costa Rica

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

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)

January 16, 2019

Primary Completion (Anticipated)

October 1, 2021

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

February 19, 2019

First Submitted That Met QC Criteria

February 20, 2019

First Posted (Actual)

February 25, 2019

Study Record Updates

Last Update Posted (Actual)

March 26, 2020

Last Update Submitted That Met QC Criteria

March 25, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R017-SABI-00126

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.

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