Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency (MESH)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00952016
Recruitment Status :
(Lack of recruitment - only 2 patients recruited.)
To assess the efficacy of methotrexate in a genetically selected population of patients with advanced colorectal cancer, who have loss of a particular gene, MSH2. The efficacy of methotrexate will be evaluated by the proportion of cases that have a significant response to treatment (objective response rate).
Condition or disease
Advanced Colorectal Cancer
The study will involve treating 29 subjects with methotrexate given intravenously. All subjects will receive treatment; there is no control arm or randomisation. The subjects will be known to have deficiency of MSH2, or a mutation (genetic change) in MSH2 that stops it functioning normally. This can either be demonstrated by testing for loss of MSH2 protein in the tumour itself, or by the demonstration of a mutation in the MSH2 gene in the subject's blood.
Objective response rate, to include complete response and partial response, as defined radiologically using RECIST (Response, Evaluation Criteria in Solid Tumours) on imaging CT scans performed during treatment.
Secondary Outcome Measures :
Disease stabilisation rate; progression free survival; 1 year survival and median overall survival; Quality of Life assessment; toxicity assessment.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Confirmed diagnosis of metastatic or locally recurrent colorectal carcinoma
Aged 18 years or older
Paraffin embedded histological material available for analysis
Either confirmed loss of expression of MSH2 on immunohistochemistry IHC or confirmed mutation in MSH2 on gene sequencing
Life expectancy of > 3 months
Previous treatment with methotrexate, either for malignant or non-malignant disease, except when methotrexate was given at low dose with other drugs to modify their effects
Concomitant uncontrolled medical conditions
Concomitant metastatic malignancy apart from non-melanotic skin cancers and carcinoma in situ of the uterine cervix in the last 10 years
Any contraindication to treatment with methotrexate (as this will affect safety)