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

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

Analysis of freely circulating DNA in liquid biopsies using the BEAMing method

Study Overview

• Status: Completed
• Conditions: RAS Wild Type mCRC

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 238

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28009
    • Research Site
  • Murcia, Spain, 30008
    • Research Site
  • Andalucía
    • Almeria, Andalucía, Spain, 04009
      • Research Site
    • Granada, Andalucía, Spain, 18014
      • Research Site
    • Sevilla, Andalucía, Spain, 41013
      • Research Site
  • Asturias
    • Aviles, Asturias, Spain, 33400
      • Research Site
    • Oviedo, Asturias, Spain, 33011
      • Research Site
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07198
      • Research Site
  • Canarias
    • La Laguna, Canarias, Spain, 38320
      • Research Site
  • Castilla León
    • Burgos, Castilla León, Spain, 09006
      • Research Site
    • Salamanca, Castilla León, Spain, 37007
      • Research Site
  • Cataluña
    • Lleida, Cataluña, Spain, 25198
      • Research Site
    • Terrassa, Cataluña, Spain, 08221
      • Research Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Research Site
    • Castellon, Comunidad Valenciana, Spain, 12002
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Research Site
    • Valencia, Comunidad Valenciana, Spain, 46015
      • Research Site
  • Extremadura
    • Caceres, Extremadura, Spain, 10003
      • Research Site
  • Galicia
    • Ourense, Galicia, Spain, 32005
      • Research Site
  • Murcia
    • Cartagena, Murcia, Spain, 30202
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects with metastatic colorectal cancer, measurable by RECIST, who start first-line treatment

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
RAS wild-type subjects; 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; 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?

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Valladares-Ayerbes M, Safont MJ, Gonzalez Flores E, Garcia-Alfonso P, Aranda E, Munoz AL, Falco Ferrer E, Cirera Nogueras L, Rodriguez-Salas N, Aparicio J, Llanos Munoz M, Pimentel Caceres PP, Castillo Trujillo OA, Vidal Tocino R, Salgado Fernandez M, Salud-Salvia A, Massuti Sureda B, Garcia-Carbonero R, Vicente Conesa MA, Lloansi Vila A; PERSEIDA investigators. Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study. Clin Transl Oncol. 2024 Apr 20. doi: 10.1007/s12094-024-03487-4. Online ahead of print.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2016
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: June 2, 2016
• First Posted (Estimated): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 20140381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR