Description:
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).
Title
- Brief Title: Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency
- Official Title: A Non-randomised Phase II Trial of Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency
Clinical Trial IDs
- ORG STUDY ID:
CCR3107
- NCT ID:
NCT00952016
Conditions
- Advanced Colorectal Cancer
Interventions
Drug | Synonyms | Arms |
---|
Methotrexate | | |
Purpose
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).
Detailed 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Eligibility Criteria
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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. |
Time Frame: | |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Disease stabilisation rate; progression free survival; 1 year survival and median overall survival; Quality of Life assessment; toxicity assessment. |
Time Frame: | |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Royal Marsden NHS Foundation Trust |
Trial Keywords
- colorectal cancer
- MSH2
- metastatic
Last Updated
October 14, 2016