Determination of RAS Mutation Status in Liquid Biopsies in Subjects With RAS Wild-type.PERSEIDA Study

Study Overview
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Brief Summary
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Analysis of freely circulating DNA in liquid biopsies using the BEAMing method

Detailed Description
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Analysis of freely circulating DNA in liquid biopsies using the BEAMing method is proposed as a technique that may be useful for analysing the RAS mutation status in different types of cancer. However, first it is necessary to evaluate the concordance between the results obtained in tumour samples and liquid biopsies. Primary objective • To evaluate the RAS mutation status at baseline in liquid biopsies in subjects with RAS wild-type metastatic colorectal cancer. Secondary objectives To evaluate the appearance of new RAS mutations using liquid biopsies at the moment of disease progression. To evaluate the appearance of new RAS mutations using liquid biopsies prior to radiological documentation of disease progression.

Official Title
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Determination of RAS Mutation Status in Liquid Biopsies in Subjects With RAS Wild-type Colorectal Cancer in First-line Treatment: a Prospective, Observational Multi-centre Study in Spain. PERSEIDA Study

Conditions
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RAS Wild Type mCRC

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects who give their informed consent in writing Subjects with metastatic colorectal cancer, measurable by RECIST, who start first-line treatment Male and female subjects, at least 18 years of age and of any ethnicity Subjects with a histologically-confirmed diagnosis of colorectal carcinoma with metastatic disease and wild-type RAS. Exclusion criteria: Pregnant or breastfeeding women Subjects who have previously received monoclonal antibodies against EGFR (cetuximab or panitumumab), small-molecule EGFR inhibitors (such as erlotinib) or other biological cancer treatments History of another solid or haematological tumour in the previous 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer Subjects who are participating or have participated in a clinical trial in the 30 days prior to inclusion.

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 |
| --- | --- |
| RAS wild-type subjects<br>The blood samples will be collected according to the site's routine clinical practice usually prior to each treatment cycle and at the follow-up visits. Analysis of the RAS mutation status will be carried out on blood samples taken at baseline, on those carried out at 20 +/-2 weeks after the start of treatment (in any case, prior to the second tumour assessment) and on the sample obtained upon progression, coinciding with routine clinical practices for collecting blood. Blood Samples will be collected to all subjects participating (119 subjects.)Objective to evaluate the RAS mutation status at baseline in liquid biopsies in subjects with RAS wild type metastatic colorectal cancer. | |
| Patient RAS WT<br>As in cohort 1 blood samples will be collected for all subjects participating (119) 10 ml will be used for analysis of the RAS mutation status. The mutation status of BRAF and EGFR will be also analysed with the IdyllaTM (Biocartis) tests in this Cohort 2. In 20 patients included in Cohort 2, 10 ml additional taken at baseline will be used in order to determine the RAS mutation status by the BEAMing technique and 10 ml additional taken at disease progression will be used to determine the mutational profile in genes other than RAS by a NGS technique. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of RAS mutations in liquid biopsies in subjects with RAS wild-type mCRC at baseline. | To evaluate the RAS mutation status at baseline in liquid biopsies in two cohorts of subjects with RAS wild-type metastatic colorectal cancer: one analysed with the BEAMing (Sysmex-Inostics) technique (Cohort 1) and the other one analysed with the IdyllaTM (Biocartis) tests (Cohort 2). | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of RAS mutations using liquid biopsies at the moment of disease progression | Serial protocol specified radiographic and clinical assessment until disease progression One (plasma DNA) liquid biopsy performed at the time progression is documented. Progression time cannot be determined in advance of it's occurrence. | Median time to progression ranges from 12 to 24 months | 
| Description of the RAS mutations using liquid biopsies at 20 +/-2 weeks after starting treatment and prior to the second radiological assessment of the disease. | The percentage of subjects who present RAS mutations in liquid biopsies taken prior to the second disease assessment will be presented. | at 20+/- 2 weeks after treatment start |