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
Conditions
Interventions
Product Name: methotrexate
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: METHOTREXATE
CAS Number: 59052
Concentration u
Sponsors
Royal Marsden Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy (by response rate using RECIST criteria) of methotrexate in patients with metastatic colorectal cancer and evidence of MSH2 deficiency previously treated with standard chemotherapy. ; Secondary Objective: To determine tumour stabilisation rates of patients receiving study treatment To determine survival of patients receiving study treatment. To determine the tolerability of study treatment in this patient population by quality of life and toxicity analysis. To identify biomarkers that may predict for a response to treatment ;Primary end point(s): The primary endpoint will be the objective response rate to treatment (ORR) (to include radiological evidence of confirmed complete response and partial response), as defined by RECIST criteria on CT scans. | — |
Countries
United Kingdom
Outcome results
None listed