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Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers

Phase 3
60 Years
Not Enrolling
Metastatic Colorectal Cancer

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Trial Information

Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers

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.

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

Type of Study:


Study Design:

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

Outcome Measure:

The primary end point is

Principal Investigator

Anders Jakobsen, Prof, MDSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Oncology, Vejle Hospital, 7100 Vejle, DK-Denmark


Denmark: National Board of Health

Study ID:




Start Date:

November 2006

Completion Date:

March 2009

Related Keywords:

  • Metastatic Colorectal Cancer
  • Metastatic colorectal cancer
  • tailored treatment
  • genetic markers
  • gene polymorphism
  • chemotherapy
  • Colorectal Neoplasms