Diagnostic Potential of Hypermethylated DNA in Colorectal Cancer

NCT02928120 | Unknown DMC

• 1 other identifier: Colomet
• Study Type: observational
• Target: 658
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of cancer-related deaths in the western world. CRC mortality is related to stage of disease with a five year survival for early-stage disease of 77.0% and 50.8% for late stage disease. Methods for early detection of primary as well as recurrent CRC are therefore important to increase patient survival. Tumour biomarkers from blood, stool, or urine could aid the early diagnostics of CRC, but despite extensive research such markers have only provided limited clinical value. Sporadic CRC develops as a result of the accumulation of genetic and epigenetic alterations. Epigenetic alterations include DNA hypermethylation, which through transcriptional silencing of tumour suppressor genes is associated with cancer development and cancer progression. The search for gene promoter regions hypermethylated in cancer has been ongoing for nearly two decades, and a number of genes have been shown to be preferentially hypermethylated in CRC. Therefore, hypermethylated DNA in plasma has been suggested as a marker for tumour-stage and survival in CRC patients. The only approved biomarker for the detection of CRC recurrence is the protein carcinoembryonic antigen (CEA). CEA is limited by its low sensitivity and therefore not recommended as a diagnostic biomarker. Hypermethylation of CRC specific genes as part of a molecular biomarker panel measured in blood could prove to be a recurrence marker in CRC patients, with elevated sensitivity and specificity. The aims of this project are to examine if hypermethylation of specific genes measured from cell-free DNA in plasma of CRC patients can be used to detect primary CRC, to detect CRC recurrence and to be a biomarker for CRC prognosis. Development of a reliable sensitive and specific biomarker for CRC will immensely improve the diagnostics and handling of CRC patients.

Conditions

Colorectal Neoplasms; Aberrant DNA Methylation

Outcome Measures

Primary Outcomes (1)

• Diagnostic potential of hypermethylated DNA as a biomarker for colorectal cancer

  Through the analysis of cell-free DNA, we will develop a diagnostic prediction model for colorectal cancer using hypermethylated DNA as a biomarker. Hypermethylation status will be analysed using real time PCR. The model will be developed using plasma samples from 193 colorectal cancer patients and 102 healthy controls. The subsequent validation of the model, will be conducted, using plasma samples from 143 colorectal cancer patients, and roughly 100 colonoscopy verified healthy controls. In the validation study, we will also analyse plasma samples from roughly 100 patients with ulcerative colitis, in order to make sure, that the model can distinguish these patients from the other groups.

  At the time of inclusion

Secondary Outcomes (2)

• Prognostic potential of hypermethylated DNA for colorectal cancer stage

  From the time of inclusion up to five years

• Hypermethylated DNA as a follow-up biomarker for disease recurrence

  From the time of inclusion and to the time of recurrence, or five years

Study Arms (5)

CRC group (exploratory)

Blood samples from approximately 210 patients diagnosed with colorectal carcinoma collected prospectively and consecutively at the Department of Surgical Gastroenterology, Aalborg University Hospital during the time period 2003-2006 will be used. The blood samples were collected at the time of diagnosis, before and after treatment (surgery and radio-chemo-therapy) and at regular intervals for a time period of two years after treatment. These blood samples were collected during a previous PhD-study: "Pre- and postoperative Venous Thromboembolism in Patients with Colorectal Cancer - implications of Radiotherapy" (ID-number VN 2003/102).

Control group (exploratory)

Blood samples (8ml) from patients (n=142) who underwent work-up for lower gastrointestinal malignancy during the time period 2003-2006. Colonoscopy was performed, and no malignancy or premalignant lesions found. Blood samples were collected before/after colonoscopy. These blood samples were collected during a previous PhD-study: "Pre- and postoperative Venous Thromboembolism in Patients with Colorectal Cancer - implications of Radiotherapy" (ID-number VN 2003/102).

CRC group (validation)

Blood samples from 143 patients were collected prospectively and consecutively for a previous study on the effect of omega 3 fatty acids an postoperative complications after colorectal surgery. All study participants have provided written informed consent (N-VN-20050035).

Control group (validation)

There will be recruited approximately 100 control subjects with a positive occult faecal blood but with a normal colonoscopy for blood sampling (28 ml).

IBD group (validation)

In collaboration with The Department of Medical Gastroenterology, Aalborg University Hospital, there will be recruited approximately 120 patients with ulcerous colitis for blood sampling (28 ml).

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

Patients with colorectal cancer, treated at Aalborg University Hospital between 2003 and 2006. Patients with colorectal cancer, treated at Aalborg University Hospital between 2007 and 2010. Patients with ulcerative colitis, followed at Aalborg University Hospital. Patients with a positive fecal occult blood test, and thereby reffered for colonoscopy in order to diagnose or rule out lower gastrointestinal cancer.

You may qualify if:

• Patients followed in the outpatient clinic with ulcerative colitis at Aalborg University Hospital.
• Patients with a positive fecal occult blood test, referred for colonoscopy

You may not qualify if:

• Prior cancer history
• Previous total colectomy

Sponsors & Collaborators

• Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery: lead

Study Sites (1)

Department of Gastrointestinal Surgery

Aalborg, 9000, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

EDTA plasma

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ole Thorlacius-Ussing, MD, DMSC

  Aalborg University Hospital

  STUDY CHAIR

Central Study Contacts

Simon L Rasmussen, MD

CONTACT

97666763; simon.rasmussen@rn.dk

June Lundtoft

CONTACT

97661131

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, DMSc

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: October 10, 2016
• Study Start: February 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2018
• Last Updated: October 10, 2016

Record last verified: 2016-10

Locations

DK (1)