Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes

NCT02198092 | Completed

• 1 other identifier: 816593
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational, case-control study evaluating the quantitative level of Septin9 in plasma pre- and post-colectomy in hereditary colorectal cancer (CRC) syndrome patients (Familial Adenomatous Polyposis (FAP), Lynch syndrome (also known as HNPCC), and Multiple Adenomatous Polyposis (MAP, also known as MYK/MYH) cases) and genetically related FAP-family members as controls and references.

Conditions

Familial Adenomatous Polyposis; Map Syndrome; Lynch Syndrome; Hnpcc; Colorectal Cancer

Keywords

familial adenomatous polyposis; multiple adenomatous polyposis; lynch syndrome; hnpcc; colorectal cancer; genetic syndrome; epigenomics; septin9

Outcome Measures

Primary Outcomes (1)

• Septin9 Plasma Levels

  The primary objective of the study is the observational analysis of quantitative Septin9 plasma levels over time in hereditary CRC syndrome patients pre- and post-colectomy.

  Up to 2 years

Secondary Outcomes (3)

• Septin9 Plasma Levels Versus Polyps

  Up to 2 years

• Pre- and Post-Colectomy Colonic Epithelial Cell Numbers

  Up to 2 years

• Septin9 Levels Versus Circulating Colonic Epithelial Cell Numbers

  Up to 2 years

Other Outcomes (2)

• Septin9 Monitoring in Individual Groups

  Up to 2 years

• Circulating Colonic Epithelial Cells at Blood Draws

  Up to 2 years

Study Arms (4)

Patient Group FAP

Clinical diagnosis of familial adenomatous polyposis (FAP). The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients. Blood draws in FAP patients should always be accompanied by blood draws in their family member controls. If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.

Other: Epi proColon Testing

Patient Group Lynch Syndrome

Clinical diagnosis of Lynch Syndrome, also known as HNPCC. The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients. If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.

Other: Epi proColon Testing

Patient Group MAP / MYH

Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon polyps. The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. The follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients. If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.

Other: Epi proColon Testing

Control Group (FAP Genetically-Related)

Genetically related family member of enrolled FAP patient. Controls, i.e. relatives of patients: Willingness to give blood at each routine follow-up as advised for the diseased relative. The patients of the control group participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating FAP patients. If colectomy is performed in a FAP patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery. Blood draws in FAP patients should always be accompanied by blood draws in their family member controls.

Other: Epi proColon Testing

Interventions

Epi proColon Testing OTHER

Plasma specimens will be collected and processed according to the Instructions for Use of the Epi proColon investigational device. For circulating colonic epithelial cell analysis, at least one ml whole blood will be required for analysis. Samples will be analyzed for circulating epithelial cells using the geometrically enhanced immunocapture device (GEDI; Gleghorn et al., 2009). Circulating epithelial cells will be captured using EpCAM antibodies and quantified by immunofluorescence microscopy as defined as cells that are DAPI+, CK+, CD45-. Captured cells will be fixed and stored at -20˚C.

Control Group (FAP Genetically-Related); Patient Group FAP; Patient Group Lynch Syndrome; Patient Group MAP / MYH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Age \> or = to 18 years of age Clinical diagnosis of familial adenomatous polyposis Clinical diagnosis of Lynch syndrome Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon polyps Genetically related family member of patients with clinical diagnosis of FAP for Control group

You may qualify if:

• Informed consent provided
• Age \> or = to 18 years of age
• Patient group FAP
• \- Clinical diagnosis of familial adenomatous polyposis
• Patient group Lynch syndrome Clinical diagnosis of Lynch syndrome
• Patient group MAP
• \- Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon polyps
• Control group (FAP)
• \- Genetically related family member of patient
• Patients: Able and willing to attend routine follow-up as advised
• Controls, i.e. relatives of patients: Willingness to give blood at each routine follow-up as advised for the diseased relative

You may not qualify if:

• Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV)
• Current diagnosis of colorectal cancer
• Pregnancy

Sponsors & Collaborators

• University of Pennsylvania: lead
• Epigenomics, Inc: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007 Oct 15;21(20):2525-38. doi: 10.1101/gad.1593107.

  PMID: 17938238 BACKGROUND

• Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 Feb;101(2):385-98. doi: 10.1111/j.1572-0241.2006.00375.x.

  PMID: 16454848 BACKGROUND

• Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008 Feb;54(2):414-23. doi: 10.1373/clinchem.2007.095992. Epub 2007 Dec 18.

  PMID: 18089654 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be used as per the study protocol. Consented subjects will provide at least 10 ml but not more than 20 ml (for repeating testing) of blood at each time point for Epi proColon testing. An additional volume of up to 10 ml anticoagulated blood will be drawn for circulating colonic epithelial cell analysis at each time point. Blood samples will be stored and will only be used in future research with the express written permission of study subjects. Subjects may withdraw consent from the study or for future use of blood samples at any time.

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Colorectal Neoplasms, Hereditary Nonpolyposis; Colorectal Neoplasms; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Rectal Diseases

Study Officials

• Bryson Katona, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: July 23, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (1)