Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency (MESH)

Royal Marsden NHS Foundation Trust

Status and phase

Terminated

Phase 2

Conditions

Advanced Colorectal Cancer

Treatments

Drug: Methotrexate

Study type

Interventional

Funder types

Other

Identifiers

NCT00952016

CCR3107

Details and patient eligibility

About

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).

Full description

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.

Enrollment

2 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)