Validation of Colon Biomarkers for the Early Detection of Colorectal Adenocarcinoma

Titre officiel

Validation and Comparison of Biomarkers for the Early Detection of Colorectal Adenocarcinoma

Sommaire:

Les chercheurs entreprennent une étude de validation multicentrique de plusieurs biomarqueurs en vue du dépistage précoce du cancer du côlon, étude à laquelle participeront 6 000 sujets. Cette étude vise à valider deux biomarqueurs fécaux (dont un panel de biomarqueurs) et un biomarqueur sérique. Les biomarqueurs seront comparés à la colonoscopie et à l’analyse immunohistochimique des selles, qui sont les tests de référence utilisés pour dépister le cancer du côlon. Il s’agit d’un projet du réseau Early Detection Research Network qui est financé par le NCI. La population cible pour cette étude est constituée des personnes qui subissent une colonoscopie de dépistage ou de surveillance systématique. Avant la colonoscopie ou dans le cadre de leur préparation pour la colonoscopie, les sujets fourniront des échantillons de sang et de selles et des données précises concernant leur appareil digestif, leurs antécédents médicaux et les médicaments qu’ils prennent. Si les sujets souhaitent participer à l’étude, des dispositions seront prises pour les rencontrer. Les chercheurs obtiendront le consentement éclairé des sujets, prélèveront un échantillon sanguin, recueilleront les données nécessaires et fourniront aux sujets une trousse de prélèvement de selles en leur expliquant la marche à suivre pour qu’ils puissent faire le prélèvement à la maison. Les établissements enverront ensuite les échantillons de selles à l’Université du Michigan à l’aide d’étiquettes UPS prépayées.

Description de l'essai

Primary Outcome:

  • Measure the sensitivity of a blood based panel of biomarkers relative to fecal immunochemical testing
Secondary Outcome:
  • To measure the specificity of a blood based panel of biomarkers relative to fecal immunochemical testing
  • To measure the sensitivity and specificity of a combined panel of blood and stool based biomarkers for the detection of colorectal cancer
The goal of this trial is to estimate the sensitivity and specificity of stool vimentin methylation, serum galectin-3 ligand, and fecal immunochemical testing for colorectal adenocarcinoma, or 2) screen relevant neoplasms (high-grade dysplasia or adenoma with ≥25% villous histologic features or adenoma measuring ≥1 cm in the greatest dimension or sessile serrated polyps measuring 1 cm or more in diameter) as single markers and in combination. Asymptomatic subjects undergoing a colonoscopic procedure for screening for colorectal cancer are eligible. Patients who have a first or second positive fecal immunochemical test, a positive stool guaiac test or a positive Cologuard test are eligible. Up to 2,500 stool blood or Cologuard positive subjects will be recruited on this protocol. Up to an additional 1,000 subjects who have not had previous FIT tests will be recruited. Subjects with a negative stool blood or Cologuard test are not eligible for enrollment. Subjects will meet with research staff prior to initiation of any colonoscopic preparative procedure. After completing informed consent, they will complete Early Detection Research Network (EDRN) data element forms. Blood and urine will be obtained following EDRN standard operating procedures (SOPs). Subjects will be provided with kits to collect stool samples for fecal immunochemical test (FIT) and processing for stool based biomarkers. The collected samples will be shipped to the Central Laboratory at the University of Michigan or German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, Germany where the stool will be homogenized, aliquoted, and stored at the Umiversity of Michigan CLASS laboratories . The FIT tests will be sent to the Central Laboratory at the University of Michigan or to DKFZ for quantitative analysis following standard operating procedures provided by Eiken Chemical Company. Data from the screening colonoscopy will be obtained. One year after colonoscopy, subjects will be contacted to determine if they have had a neoplastic colorectal diagnosis or other neoplastic events. Data management and protocol coordination will be performed by the Data Management and Coordinating Centre (DMCC) of the EDRN along with the GLNE Prevention Research Base at the University of Michigan and will include a Web-based front end and relational database backend, with biosample tracking (VSIMS). Biosamples will be managed in a high quality repository facility at the University of Michigan. We will estimate sensitivities and specificities and the corresponding confidence intervals of the stool DNA tests and serum/plasma tests for detection of invasive colorectal neoplasms and for screen relevant neoplasias (Aim 1). We will then test the primary hypothesis to confirm the clinical accuracy of a particular biomarker test or panel (Aim 2). The specific primary hypothesis will be defined prior to data analysis based on state of the art information available at that time about candidate biomarkers and tests. Several specific examples of potential primary hypotheses are given to justify study sample size. Finally, several alternative tests and multi-marker panels will be evaluated. (Aim 3). In secondary analysis, we will (a) provide measures of diagnostic accuracy standardized to the age and gender distribution of US population and (b) assess the effect of subject heterogeneity on the marker performance. A primary objective is to establish an archive of appropriately preserved stool, serum, plasma and DNA human biospecimens to be used by EDRN-approved investigators for future validation and biomarker discovery research (Aim 4).

Voir cet essai sur ClinicalTrials.gov

Intéressé(e) par cet essai?

Imprimez cette page et apportez-la chez votre médecin pour discuter de votre admissibilité à cet essai et des options de traitement. Seul votre médecin peut vous recommander pour un essai clinique.

Ressources

Société canadienne du cancer

Ces ressources sont fournies en partenariat avec Société canadienne du cancer