Clinical trial NCT03852290: C677T and A1298C MTHFR Polymorphisms and Fluoropyrimidine Effectiveness in Metastatic Colon Cancer
Official title: Association of the C677T and A1298C MTHFR Polymorphisms With Chemotherapy Effectiveness Among Patients With Metastatic Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colon Cancer
MTHFR Gene Mutation
Chemotherapeutic Toxicity
Chemotherapy Effect
Keywords: Colon cancer
Fluoropyrimidine
Lead sponsor: Universidad de Costa Rica
Sponsor class: OTHER
Collaborators: name: Universitat Autonoma de Barcelona
First posted: 2019-02-25
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 50 patients with metastatic colorectal cancer treated with any fluoropyrimidine.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of C677T and A1298C MTHFR polymorphisms and overall survival
timeFrame: From the start date of treatment until the date of death from any cause, assessed up to 24 months
measure: Assessment of C677T and A1298C MTHFR polymorphisms and progression-free survival
timeFrame: 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
measure: Assessment of C677T and A1298C MTHFR polymorphisms and response rate
timeFrame: From the start date of treatment until the first radiological or clinical assessment, up to 6 months.
Secondary outcomes:
measure: Assessment of C677T and A1298 MTHFR polymorphisms and toxicity
timeFrame: 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)
Other outcomes:
Locations:
city: San José
country: Costa Rica
facility: Hospital San Juan de Dios
Study officials:
affiliation: Universidad de Costa Rica
name: Allan Ramos-Esquivel, Mic
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramos-Esquivel A, Chinchilla-Monge R, Abbas J, Valle M. C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in Mestizo patients with metastatic colorectal cancer. Pharmacogenet Genomics. 2021 Dec 1;31(9):191-199. doi: 10.1097/FPC.0000000000000440.