Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency

Advanced Colorectal Cancer Clinical Trial

— MESH  

Official title:

A Non-randomised Phase II Trial of Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00952016
• Other study ID #: CCR3107
• Status: Terminated
• Phase: Phase 2
• First received: July 31, 2009
• Last updated: October 13, 2016
• Start date: February 2009
• Est. completion date: September 2014

Study information

• Verified date: August 2009
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Methotrexate
study subjects will receive methotrexate intravenously on day 1 and day 8 of a 3 weekly cycle.

Locations

Country	Name	City	State
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease stabilisation rate; progression free survival; 1 year survival and median overall survival; Quality of Life assessment; toxicity assessment.