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

• Conditions: Colon Cancer; Chemotherapy Effect; MTHFR Gene Mutation; Chemotherapeutic Toxicity

• Registration Number: NCT03852290
• Lead Sponsor: Universidad de Costa Rica

Brief Summary

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.

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 Timeline

• Study Start: 2019-01-16
• Study First Submitted: 2019-02-19
• Study First Submitted QC: 2019-02-20
• Study First Posted: 2019-02-25
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-25
• Last Update Posted: 2020-03-26
• Primary Completion: 2021-10-01
• Study Completion: 2021-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 65

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Assessment of C677T and A1298 MTHFR polymorphisms and toxicity	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

Trial Locations

Locations (1)

Hospital San Juan de Dios; 🇨🇷 San José, Costa Rica