Colon CancerNCT03852290
C677T and A1298C MTHFR Polymorphisms and Fluoropyrimidine Effectiveness in Metastatic Colon Cancer
An observational study of Colon Cancer and MTHFR Gene Mutation, run by Universidad de Costa Rica at 1 site in Costa Rica.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, MTHFR Gene Mutation, Chemotherapeutic Toxicity
- How many people
- 65 participants
- Where
- 1 siteCosta Rica
- Study dates
- 16 Jan 2019to 1 Oct 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 50 patients with metastatic colorectal cancer treated with any fluoropyrimidine.
Who may be able to join
- 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.
Who cannot join
- Any other malignant condition
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Keywords
- Colon cancer, Fluoropyrimidine
- Medical subject headings
- Colonic Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of C677T and A1298C MTHFR polymorphisms and overall survival
Overall survival
Measured: 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
Progression-Free survival
Measured: 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
Response rate
Measured: From the start date of treatment until the first radiological or clinical assessment, up to 6 months.
Secondary outcomes (1)
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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2019
- Study start16 Jan 2019
- Primary completion1 Oct 2021 (estimated)
- Study completion1 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad de Costa Rica
- Sponsor type
- University, hospital or other
- Collaborators
- Universitat Autonoma de Barcelona
- Responsible party
- Principal investigator, Allan Ramos-Esquivel, Universidad de Costa Rica
- Investigators
- Allan Ramos-Esquivel, Mic, Principal investigator, Universidad de Costa Rica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03852290
- Sponsor's protocol ID
- R017-SABI-00126
- Status last verified
- Mar 2020
- First submitted
- 19 Feb 2019
- Last updated
- 26 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34116533
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of the C677T and A1298C MTHFR Polymorphisms With Chemotherapy Effectiveness Among Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03852290
- Acronym / sponsor ID
- R017-SABI-00126
- Keywords
- Colon cancer, Fluoropyrimidine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Universidad de Costa RicaUniversity, hospital or other
- Collaborators
- Universitat Autonoma de Barcelona
- Study start
- 16 Jan 2019 (actual)
- Primary completion
- 1 Oct 2021 (estimated)
- Study completion
- 1 Oct 2021 (estimated)
- First posted
- 25 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 50 patients with metastatic colorectal cancer treated with any fluoropyrimidine.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Any other malignant condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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
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
1 secondary outcome
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2020.
- Derived from this study: PubMed 34116533Ramos-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan Ramos-Esquivel, Mic principal investigator
Universidad de Costa Rica
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colon Cancer and MTHFR Gene Mutation, run by Universidad de Costa Rica at 1 site in Costa Rica.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Costa Rica. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03852290, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020.