Tailored Treatment in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00396487
• Other study ID #: TT-2006-002957-56
• Status: Terminated
• Phase: Phase 3
• First received: November 6, 2006
• Last updated: June 10, 2015
• Start date: November 2006
• Est. completion date: February 2008

Study information

• Verified date: June 2015
• Source: Vejle Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Capecitabine, Irinotecan, 5-Fluorouracil+Calciumfolinat

Locations

Country	Name	City	State
Denmark	Aalborg Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Sydvestjysk Hospital Esbjerg	Esbjerg
Denmark	Herlev Hospital	Herlev
Denmark	Herning Central Hospital	Herning
Denmark	Næstved Hospital	Næstved
Denmark	Odense University Hospital	Odense
Denmark	Roskilde Hospital	Roskilde
Denmark	Viborg Hospital	Viborg

Sponsors (1)

Lead Sponsor	Collaborator
Vejle Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point is
Primary	Response according to RECIST criteria.
Secondary	Secondary end points are
Secondary	Progression free survival
Secondary	Overall survival
Secondary	Toxicity