Tailored Treatment in Metastatic Colorectal Cancer

Vejle Hospital

Status and phase

Terminated

Phase 3

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Capecitabine, Irinotecan, 5-Fluorouracil+Calciumfolinat

Study type

Interventional

Funder types

Other

Identifiers

NCT00396487

TT-2006-002957-56

Details and patient eligibility

About

To compare the response rate of single agent chemotherapy in advanced colorectal cancer given as standard treatment versus tailored treatment in a randomised phase III trial.

Full description

The TS and MTHFR polymorphism has been investigated in a new study based on analysis of normal tissue. The results indicated that protein with a 3/3 TS polymorphism or a MTHFR T polymorphism had a significantly higher response rate and a longer time to progression than the other groups when treated with bolus 5-FU.

Capecitabine is metabolised to 5-FU through a number of enzymatic steps. It is the first rationally designed drug that is based upon the high concentration of thymidine phosphorylase (TP) in many human tumors compared to normal tissue. TP is the last step in the conversion of capecitabine to 5-FU and seems to be the limiting factor for the activation. Capecitabine may to some extent mimic continues 5-FU infusion as opposed to bolus 5-FU. A number of small investigations have indicated that patients with 2R/2R TS polymorphism have a higher response rate than heterozygous patients.

The TS and MTHFR polymorphism analysis can easily be performed on sputum, which means an easy collection and sending of the samples.

At present single agent chemotherapy is based on three drugs (5-FU, capecitabine, and Irinotecan) with almost the same overall activity. It seems rational to investigate if improvement can be obtained by tailoring the treatment according to gene polymorphism.

Enrollment

1 patient

Sex

All

Ages

60+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Metastatic colorectal cancer
Histopathological verification of the primary tumor
Measurable disease according to RESIST criteria
Single agent chemotherapy indicated
Performance status >=2
Age >= 60 years
Life expectancy > 3 months
Adequate liver and kidney function as evaluated by bilirubin <= 3 times of normal upper limit, ALAT <= 3 times upper normal limit (<= 5 times upper normal limit in case of liver metastases), serum creatinine <= 1.5 times normal upper limit.
ANC >=1.5 x 109/l and platelets >= 100 x 109/l
Informed consent

Exclusion criteria

Patients with CNS metastases
Other malignant disease within the last 5 years except for non-melanoma skin cancer and carcinoma in situ of cervix uteri
Previous chemotherapy for metastatic disease
Adjuvant chemotherapy < 6 months before inclusion
Patients with previous major toxic or allergic reaction to the protocol drugs