MESH: A Non-Randomised Phase II Trial of Methotrexate in Metastatic Colorectal Cancer with MSH2 Deficiency - MESH

Phase 1

• Conditions: Metastatic colorectal cancer resistanct to standard chemotherapy with evidence of deficiency of the mismatch repair gene MSH2, either on immunohistochemistry of tumour histology or on testing of peripheral blood for a germline mutation in MSH2; MedDRA version: 9.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer

• Registration Number: EUCTR2008-000524-82-GB
• Lead Sponsor: Royal Marsden Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-12-09
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 29

Inclusion Criteria

1) Confirmed diagnosis of metastatic or locally recurrent colorectal carcinoma
2) Paraffin embedded histological material available for analysis
3) Either confirmed loss of expression of MSH2 on IHC or confirmed mutation in MSH2 on gene sequencing
4) Life expectancy of > 3 months
5) ECOG Performance Status of 0-2
6) Willingness and ability to comply with scheduled study visits and tests
7) Radiologically and/ or clinically documented measurable disease (RECIST criteria)
8) Adequate bone marrow function, renal function and hepatic function
9) Metastatic disease refractory to standard chemotherapy with 5-fluorouracil, irinotecan and oxaliplatin containing regimens, or intolerant of standard chemotherapy, or other patient factors why standard treatment cannot be given
10) Age 18 years or older
11) Patients must be willing to undertake appropriate contraceptive methods or remain sexually abstinent for the duration of study treatment and for at least three months after receiving the last dose of chemotherapy

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Previous treatment with methotrexate, either for malignant or non-malignant disease, except when methotrexate was given as a chemomodulator with 5-fluorouracil for colorectal cancer in the adjuvant setting
2) Concomitant uncontrolled medical conditions
3) Concomitant metastatic malignancy apart from non-melanotic skin cancers and carcinoma in situ of the uterine cervix in the last 10 years
(Previous treatment for cancers associated with the Lynch syndrome is acceptable)
4) Pregnant or breast feeding
5) Medical or psychiatric conditions impairing ability to give informed consent
6) Any contraindication to treatment with methotrexate
7) Prior radiotherapy to a lesion that will be used as a marker lesion to assess disease response, unless there has been evidence of clear documented progression of that lesion since radiotherapy
8) Consideration should be given to treating significant 3rd compartment fluid collections (ascites, pleural effusions) before treatment commences

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified