SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03852290

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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.

NCT03852290 Colon Cancer MTHFR Gene Mutation Chemotherapeutic Toxicity Chemotherapy Effect
MeSH: Colonic Neoplasms
HPO: Colon cancer Neoplasm of the colon


Primary Outcomes

Description: Overall survival

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and overall survival

Time: From the start date of treatment until the date of death from any cause, assessed up to 24 months

Description: Progression-Free survival

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and progression-free survival

Time: 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

Description: Response rate

Measure: Assessment of C677T and A1298C MTHFR polymorphisms and response rate

Time: From the start date of treatment until the first radiological or clinical assessment, up to 6 months.

Secondary Outcomes

Description: 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

Measure: Assessment of C677T and A1298 MTHFR polymorphisms and toxicity

Time: 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)

Time Perspective: Prospective

Cohort


There are 2 SNPs

SNPs


1 rs18011131

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.


2 rs1801133

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.



HPO Nodes


HPO:
Colon cancer
Genes 39
FOXE1 PMS1 APC MLH1 CDKN2A KRAS PRKAR1A FLCN TGFBR2 MSH6 COL14A1 RPS19 BMPR1A HABP2 PMS2 MSH2 MSH3 MLH3 GREM1 MINPP1 BRCA1 BUB3 BRCA2 CEP57 AAGAB TRIP13 EPCAM PIK3CA PALLD NTHL1 PALB2 MUTYH TP53 AXIN2 SMAD4 BUB1 SH3KBP1 BUB1B FAN1
Neoplasm of the colon
Genes 54
FOXE1 PMS1 CDKN2A KRAS TGFBR2 STK11 MSH6 BMPR1A PMS2 MLH3 BRCA1 BRCA2 PDGFRA PIK3CA POLD1 NTHL1 POLE BUB1 SH3KBP1 BUB1B CHEK2 APC MLH1 PRKAR1A FLCN COL14A1 RPS19 RPS20 HABP2 MSH2 MSH3 GREM1 MINPP1 SEMA4A BUB3 PTEN MDM2 CEP57 ENG AAGAB TRIP13 KIT EPCAM RNF43 PALLD PALB2 MUTYH SDHA TP53 SDHB SDHC AXIN2 SMAD4 FAN1