Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes (Septin9)

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Lynch Syndrome; Familial Adenomatous Polyposis; Map Syndrome; Hnpcc
• Intervention / Treatment: Other: Epi proColon Testing

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.
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; 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.
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; 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); 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Septin9 Plasma Levels Versus Polyps	• Correlation of quantitative Septin9 plasma levels with the approx. number of polyps	Up to 2 years
Pre- and Post-Colectomy Colonic Epithelial Cell Numbers	• Correlation of circulating colonic epithelial cell number pre- and post-colectomy	Up to 2 years
Septin9 Levels Versus Circulating Colonic Epithelial Cell Numbers	• Correlation of circulating colonic epithelial cell number with Septin9 levels	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Septin9 Monitoring in Individual Groups	The primary endpoint of the study is the completion of Septin9 monitoring in the individual patient disease groups (or family controls) over a period of two years or in case of colectomy within 28 days after colectomy. The endpoint is defined as the documented receipt of blood draws at least every six months on the scheduled healthcare visit at the institute after enrollment over the two years participation period. If any patient needs to undergo colectomy within the two years of study participation, the endpoint is defined as documented receipt of both blood draws occured prior to any surgical bowel preparation and 28 days at the latest after surgery.	Up to 2 years
Circulating Colonic Epithelial Cells at Blood Draws	The secondary endpoints of the study are the documented results of the circulating colonic epithelial cell numbers for each blood draw performed.	Up to 2 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Epigenomics, Inc
• Investigators: Principal Investigator: Bryson Katona, MD, University of Pennsylvania

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): August 1, 2019
• Study Completion (ACTUAL): August 1, 2019

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (ESTIMATE): July 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: colorectal cancer; familial adenomatous polyposis; epigenomics; lynch syndrome; multiple adenomatous polyposis; hnpcc; genetic syndrome; septin9
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Adenomatous Polyps; Adenoma; Intestinal Polyposis; Syndrome; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Adenomatous Polyposis Coli
• Other Study ID Numbers: 816593