Response Prediction in Metastasized Colorectal Cancer Using Intratumoral Thymidylate Synthase

Study Overview
=================
Brief Summary
-----------------
The aim of the study was to evaluate the feasibility of TS determination in a multicenter trial setting using a central facility for measurement and confirm its role as predictive factor for 5-FU treatment in MCRC.

Detailed Description
-----------------
Eligible were patients with non-resectable metastasized or recurrent histologically proven CRC with the presence of a reference lesion two-dimensional measurable and accessible for a biopsy.The biopsy was taken from the reference lesion either by surgery during primary tumor resection, by trans-cutaneous true-cut needle biopsy or by trans-anal approach. Intratumoral relative TS mRNA expression levels were determined using samples shipped in RNA-preserving solution or as glass slides after microdissection of tumor cells. An independent company stratified the patients according to ther relative TS mRNA expression level in TS low and TS high followed by randomization to receive either FUFA of Folfiri. Response to chemotherapy was evaluated and documented according to the RECIST criteria after every therapy cycle.

Official Title
-----------------
Stratified and Randomized Multi-center Phase II - to Determine Potential Benefit of Treating Patients With Advanced Colorectal Cancer According to the Intratumoral TS RNA Levels

Conditions
-----------------
Colorectal Cancer, Non Resectable Metastasis, Reference Lesion, Biopsy, Thymidylate Synthase Quantitation

Intervention / Treatment
-----------------
* Drug: FUFA
* Drug: systemic chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients (>= 18 years) with non-resectable metastasized or recurrent histologically proven CRC with the presence of a reference lesion two-dimensional measurable and accessible for a biopsy a performance status WHO 0-2 (Karnofsky >= 60%) an estimated life expectancy of at least 3 months written informed consent Exclusion Criteria: patients older than 75 years not fulfilling these criteria brain metastases or a secondary cane a history of a systemic palliative chemotherapy and an adjuvant chemotherapy (within 6 months) pregnant or nursing women a known allergy toward irinotecanhydroclorid or of any ingredients of Campto or other severe medical laboratory and social conditions not allowing chemotherapy and follow-up

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-FU<br>FUFA 5-flurouracil and folinic acid control | Drug: FUFA<br>* 2600/500 mg/m2 i.v. 24 h via port, 1 time weekly for six weeks, than have a break for 2 weeks (=8 weeks for 1 cycle)<br>|
| Active Comparator: Folfiri<br>5-fluouracil and folinic acid in combination with irinotecan (Folfiri) systemic chemotherapy intensified treatment arm | Drug: systemic chemotherapy<br>* CPT-11, 80 mg/m2 for 90 minutes and 5 FU/FA 2000/500 mg/m2 iv. 24h via port; 1 time weekly for six weeks, than have a break for 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response to first-line chemotherapy (recist) | Response to chemotherapy was evaluated and documented according to the RECIST criteria after every therapy cycle (every two months). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival, toxicity, treatment related complications, time to progression | See above. | 3-year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal Cancer, non resectable metastasis, reference lesion, biopsy, thymidylate synthase quantitation