Observational Study to Evaluate the Use of Targeted Therapies in Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate, in terms of overall survival, the benefit of monoclonal antibodies in the start time of the diagnosis of advanced disease or administer a deferred basis after progression to treatment with chemotherapy alone. Initially expected target population was 1950 patients (pts), in 2015 protocol was ammended to 1028 patients, because the size was sufficient to evaluate the superiority of the use of monoclonal antibodies the start time of the diagnosis against deferred use, with HR of 0.8, power of 90% and an alpha of 0.05. Finally in July 2018, recruitment was completed with a total of 1104 patients enrolled.

Official Title
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Observational Study to Evaluate the Use of Targeted Therapies in Metastatic Colorectal Cancer

Conditions
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Metastatic Colon Cancer

Intervention / Treatment
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* Drug: Chemotherapy
* Biological: Chemotherapy plus monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with metastatic colorectal cancer with biopsy positive for adenocarcinoma. ECOG PS0-2. Who have not received prior chemotherapy treatment for metastatic disease. Measurable or evaluable disease. No previous surgery for metastatic disease. Surgery for metastasis allowed after inclusion in the study aftercare at the discretion of investigadors. Chemotherapy treatment with doublets (CAPOX, FOLFOX, FOLFIRI) Exclusion Criteria: Patients older than 70 years with frailty criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active comparator: Chemotherapy<br>Metastatic colon cancer and first line treatment with conventional chemotherapy without monoclonal antibody. | Drug: Chemotherapy<br>* Metastatic colon cancer, first line treatment with conventional chemotherapy<br>* Other names: Standard Chemotherapy;|
| Experimental: Chemotherapy plus mAb<br>Metastatic colon cancer and first line treatment with conventional chemotherapy plus monoclonal antibody | Biological: Chemotherapy plus monoclonal antibody<br>* Metastatic colon cancer, first line treatment with conventional chemotherapy plus monoclonal antibody<br>* Other names: Standard CHemotherapy plus monoclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From date of inclusion until the date of death from any cause. | From July 2018 (LPI), 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate prognostic score GEMCAD | The two main prognostic scores for metastatic colorectal cancer (Kohne and GERCOR) do not account for resectability of liver-only metastasis (LiM) and thus are limited as treatment guidance. We propose a classification of patients based on LiM resectability, performance status (PS) and lactate dehydrogenase (LDH) levels and compare its discrimination capacity against Kohne and GERCOR scores. GEMCAD score: patients are classified as stage 1 if LiM are considered resectable (<4 nodules and <5 cm diameter) or potentially resectable (>4 and <10 nodules or >5 cm diameter), PS 0-1 and LDH < 1.5 ULN; stage 2 if LiM are not resectable or with extrahepatic spread, PS 0-1 and LDH < 1.5 ULN; stage3 if PS 2 or LDH > 1.5 ULN. This score, Kohne, and GERCOR scores will be tested for discrimination using Harrel's C index (HCI, higher is better) and calibration using Akaike information criterion (AIC, smaller is better) of progression-free survival (PFS) and overall survival (OS). | From August 2014, up to 36 months | 
| To compare GERCOR and Köhne classification with GEMCAD classification | The two main prognostic scores for metastatic colorectal cancer (Kohne and GERCOR) do not account for resectability of liver-only metastasis (LiM) and thus are limited as treatment guidance. We propose a classification of patients based on LiM resectability, performance status (PS) and lactate dehydrogenase (LDH) levels and compare its discrimination capacity against Kohne and GERCOR scores. This score, Kohne, and GERCOR scores will be tested for discrimination using Harrel's C index (HCI, higher is better) and calibration using Akaike information criterion (AIC, smaller is better) of progression-free survival (PFS) and overall survival (OS). | From August 2014, up to 36 months | 
| Evaluate Sadananda cellular phenotype classification |  | From August 2014, up to 36 months | 
| Study other variables to identify whether there is group of patients who may benefit from monoclonal antibodies for the treatment of first-line chemotherapy | Study whether there are demographic variables, analytical or related tumor and its extension to allow us to identify whether there is group of patients who may benefit from monoclonal antibodies for the treatment of first-line chemotherapy | From August 2014, up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Colon Cancer, Monoclonal antibodies, Chemotherapy, First line