Back to resultsMethotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency (MESH)
Primary Purpose
Advanced Colorectal Cancer
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Colorectal Cancer focused on measuring colorectal cancer, MSH2, metastatic
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)
Sites / Locations
- The Royal Marsden NHS Foundation Trust
Outcomes
Primary Outcome Measures
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.
Full Information
NCT ID
NCT00952016
First Posted
July 31, 2009
Last Updated
October 13, 2016
Sponsor
Royal Marsden NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT00952016
Brief Title
Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency
Acronym
MESH
Official Title
A Non-randomised Phase II Trial of Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
August 2009
Overall Recruitment Status
Terminated
Why Stopped
Lack of recruitment - only 2 patients recruited.
Study Start Date
February 2009 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Royal Marsden NHS Foundation Trust
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Colorectal Cancer
Keywords
colorectal cancer, MSH2, metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
study subjects will receive methotrexate intravenously on day 1 and day 8 of a 3 weekly cycle.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Disease stabilisation rate; progression free survival; 1 year survival and median overall survival; Quality of Life assessment; toxicity assessment.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Facility Information:
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
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Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency
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