Clinical trial NCT00396487: Tailored Treatment in Metastatic Colorectal Cancer
Official title: Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic colorectal cancer
tailored treatment
genetic markers
gene polymorphism
chemotherapy
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2006-11-07
Enrollment: 1
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The primary end point is
measure: Response according to RECIST criteria.
Secondary outcomes:
measure: Secondary end points are
measure: Progression free survival
measure: Overall survival
measure: Toxicity
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Esbjerg
country: Denmark
facility: Sydvestjysk Hospital Esbjerg
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herning
country: Denmark
facility: Herning Central Hospital
city: Næstved
country: Denmark
facility: Næstved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Viborg
country: Denmark
facility: Viborg Hospital
Study officials:
affiliation: Department of Oncology, Vejle Hospital, 7100 Vejle, DK-Denmark
name: Anders Jakobsen, Prof, MDSc
role: PRINCIPAL_INVESTIGATOR
References: