Tailored Treatment in Metastatic Colorectal Cancer

Phase 3

Terminated

• Conditions: Metastatic Colorectal Cancer

• Registration Number: NCT00396487
• Lead Sponsor: Vejle Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2006-11
• Study First Submitted: 2006-11-06
• Study First Submitted QC: 2006-11-06
• Study First Posted: 2006-11-07
• Study Completion: 2008-02
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-10
• Last Update Posted: 2015-06-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary end point is
Response according to RECIST criteria.

Secondary Outcome Measures

Name	Time	Method
Secondary end points are
Progression free survival
Overall survival
Toxicity

Trial Locations

Locations (10)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Herlev Hospital; 🇩🇰 Herlev, Denmark

Herning Central Hospital; 🇩🇰 Herning, Denmark

Næstved Hospital; 🇩🇰 Næstved, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Viborg Hospital; 🇩🇰 Viborg, Denmark

Aalborg Hospital; 🇩🇰 Aalborg, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Sydvestjysk Hospital Esbjerg; 🇩🇰 Esbjerg, Denmark

Roskilde Hospital; 🇩🇰 Roskilde, Denmark