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

Colon Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03852290
• Other study ID #: R017-SABI-00126
• Status: Active, not recruiting
• Start date: January 16, 2019
• Est. completion date: October 1, 2021

Study information

• Verified date: March 2020
• Source: Universidad de Costa Rica
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: October 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapeutic Toxicity
• Chemotherapy Effect
• Colon Cancer
• Colonic Neoplasms
• MTHFR Gene Mutation

Locations

Country	Name	City	State
Costa Rica	Hospital San Juan de Dios	San José

Sponsors (2)

Lead Sponsor	Collaborator
Universidad de Costa Rica	Universitat Autonoma de Barcelona

Country where clinical trial is conducted

Costa Rica, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of C677T and A1298C MTHFR polymorphisms and overall survival	Overall survival	From the start date of treatment until the date of death from any cause, assessed up to 24 months
Primary	Assessment of C677T and A1298C MTHFR polymorphisms and progression-free survival	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
Primary	Assessment of C677T and A1298C MTHFR polymorphisms and response rate	Response rate	From the start date of treatment until the first radiological or clinical assessment, up to 6 months.
Secondary	Assessment of C677T and A1298 MTHFR polymorphisms and toxicity	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)