Correlation Between Circulating Tumour Markers Early Variations and Clinical Response in First Line Treatment of Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
The chemotherapy monitoring is currently based on radiological (RECIST 1.1 guideline) and clinical evaluation every 3 months. Circulating markers as Carcino Embryonic Antigen (CEA), circulating tumour DNA and total cell free DNA represent an alternative approach to evaluate the response. In the field of metastatic colorectal cancer (mCRC) recent studies suggest that early evaluation could be clinically relevant. Indeed, early tumoral response seems to be correlated to overall survival. Moreover, post-operative morbidity increases with the number of prior chemotherapy treatments. Early evaluation could allow to modify chemotherapy regimens when response appears to be insufficient. The aim of the present study is to evaluate, in a prospective cohort of patients treated with systemic IV chemotherapy (5 Fluorouracil +/- oxaliplatin +/- irinotecan) +/- targeted therapy as first line treatment for a mCRC, the correlation between early variations of circulating tumour markers including CEA, circulating tumour DNA and total cell free DNA, and the 3 months objective response as defined in the RECIST 1.1 guideline.

Official Title
-----------------
Correlation Between Circulating Tumour Markers Early Variations and Clinical Response in First Line Treatment of Metastatic Colorectal Cancer

Conditions
-----------------
Circulating Markers, Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Procedure: Blood sampling for free mutant DNA analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age superior to 18 years. Histologically confirmed metastatic colorectal adenocarcinoma. Measurable disease according to the RECIST 1.1 guideline ECOG performance status <3. Disease requiring IV chemotherapy (5 Fluorouracil +/- oxaliplatin +/- irinotecan) +/- targeted therapy (cetuximab or panitumumab or bevacizumab) every 14 days No prior chemotherapy for this adenocarcinoma with the exception of adjuvant chemotherapy Signed and dated informed consent document. Exclusion Criteria: Medical history of cancer within 5 years Medical contraindication for a treatment consisted of IV chemotherapy (5 Fluorouracil +/- oxaliplatin +/- irinotecan) +/- targeted therapy (cetuximab or panitumumab or bevacizumab) Patient with known psychiatric or substance abuse disorders that could interfere with cooperation with the requirements of the study

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

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

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

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

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients Treated for Metastatic Colorectal cancer<br>Blood sampling for free mutant DNA analysis for Patients Treated for Metastatic Colorectal cancer | Procedure: Blood sampling for free mutant DNA analysis<br>* Blood sampling for Patients Treated for Metastatic Colorectal cancer<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference from baseline in the number of free mutant DNA in blood | Variation of free mutant DNA kinetic at week 5 to predict tumor progression at 3 months (Evaluation based on the RECIST 1.1 guideline) | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference from baseline in the number of free mutant DNA in blood | Variation of free mutant DNA kinetic at week 3 to predict tumor progression at 3 months (Evaluation based on the RECIST 1.1 guideline) | 3 weeks | 
| Evaluation of response based on the RECIST 1.1 guideline | sensitivity and specificity of free mutant DNA kinetic at Week 5 (RECIST) to predict tumor progression at 3 months (RECIST) | 3 Months |