Diagnosis of Colorectal Cancer and Advanced Adenoma Using Cancer-specific Methylation Signatures

NCT03828396 | Unknown

• 1 other identifier: B2018-116R2
• Study Type: observational
• Target: 1,300
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer is a common malignant tumor of the digestive tract. It is still a challenging task to detect colorectal cancer at an early stage. Studies have found that DNA methylation has a relationship with the occurrence and development of tumors. Singlera Genomics Inc. has invented the proprietary methyl-Titan sequencing technology and developed a detection method for colorectal cancer and advanced adenoma (Adenoma/Colorectal cancer Early detection, ACE) using the cancer-specific methylation markers. ACE is a blood-based non-invasive diagnostic technique. It has high compliance rate compared with colonoscopy, and sampling is more convenient than stool testing. It also has much higher sensitivity compared to existing blood testing methods. The current study plans to use ACE method to analyze ctDNA in the blood for the cancer-specific DNA methylation markers to aid in the differential diagnosis of patients with colorectal cancer or adenoma. This technique will greatly reduce the discomfort in the diagnosis of suspected patients and improve the diagnosis of high-risk population of colorectal cancer. The goals of this study are: 1) to establish a detection system based on plasma ctDNA methylation sequencing technology for the auxiliary diagnosis of colorectal cancer and adenoma, 2) to assess the diagnostic value of plasma ctDNA methylation signature for colorectal cancer and adenoma, and 3) to assess the association of plasma ctDNA methylation signals with colonoscopy results and pathological results of surgical specimens. A total of 1300 patients (700 cases positive and 600 cases negative) aging between 45 and 80 years old will be enrolled. Colonoscopy will be performed to determine whether patients are positive or negative. Positive patients who need surgical resection will be further classified according to their surgical histopathological results. For negative patients, the type of lesion will be clarified. The plasma samples of all subjects will be analyzed for cancer-specific ctDNA methylation profiles. Based on the results of plasma ctDNA methylation test, the risks of colorectal cancer of the enrolled subjects are scored. Combined with the grouping information, the clinical application value of the cancer-specific methylation profile for early cancer diagnosis will be assessed.

Conditions

Colorectal Cancer; Advanced Adenoma

Keywords

DNA methylation; Next generation sequencing

Outcome Measures

Primary Outcomes (1)

• Assay sensitivity and specificity for colorectal cancer and advanced adenoma

  Assay sensitivity and specificity will be determined using colonoscopy and histopathological results as the gold standard. The following formula will be used to calculate sensitivity and specificity: sensitivity= TP/(TP+FN); specificity= TN/(TN+FP)

  August 17, 2018- September 30, 2020

Study Arms (2)

High risk (positive)

Colorectal cancer and advanced adenoma

Low risk (Negative)

Healthy people and other colorectal diseases

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Positive Colorectal Cancer, all stages (I-IV), any size Advanced adenoma, including the following subcategories： High grade dysplasia，any size； Adenoma, villous growth pattern (\>25%), any size； Tubular adenoma，\> 1.0 cm； Serrated lesion，\> 1.0 cm Negative Non-advanced adenoma, ≤10mm, Inflammatory colorectal disease, benign hyperplasia, tumor-free patients upon histopathological review, Normal healthy people

You may qualify if:

• Age 45\~80 years old, gender is not limited, women are not in pregnancy and lactation;
• Willing to accept a full colonoscopy;
• The patients enrolled are newly diagnosed patients who did not receive surgery, radiotherapy, chemotherapy, targeted therapy or other tumor-related intervention;
• The anticoagulant drugs such as warfarin, aspirin and Plavix were stopped for 1 week, and low molecular weight heparin was stopped on the same day;
• No history of other cancer diseases, normal liver and kidney function;
• No major trauma requiring blood transfusion treatment occurred within one week.

You may not qualify if:

• Have had colorectal cancer or intestinal adenoma before;
• Have other cancer history;
• Previously undergoing a colon and rectal resection (except for sigmoid diverticulosis);
• Patients with Lynch syndrome in the family;
• History of severe cardiovascular disease (eg previous myocardial infarction, coronary artery bypass grafting or coronary stenting, history of congestive heart failure; myocardial infarction within 6 months, uncontrolled severe hypertension, etc.), or patients that the investigator determines not suitable for enrollment;
• Participated in "interventional" clinical trials and have taken test drugs over the past 30 days;
• Patients that the investigator determines not suitable for enrollment;
• Failure to follow the test plan to collect blood on time;
• The blood collection sample does not meet the requirements.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• West China Hospital: collaborator
• Guangzhou First People's Hospital: collaborator
• Dalian University Affiliated Xinhua Hospital: collaborator
• Fudan University: collaborator
• Singlera Genomics Inc.: collaborator

Study Sites (1)

Shanghai Zhongshang Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (1)

• 1. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med, 2013; 369(12): 1106-1114. 2. Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer, 2013, 49(14): 3049-3054. 3. National Cancer Institute's SEER database. [EB/OL]. http://seer.cancer.gov/. Accessed August 26, 2016. 4. M. Esteller. Molecular origins of cancer: epigenetics in cancer. New Engl J Med, 2008; 358(11): 1148-1096. 5. D. J. Weisenberger, K. D. Siegmund, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nature Genetics, 2006; 38(7): 787-793. 6. E. E. Torlakovic, J. D. Gomez, et al. Sessile serrated adenoma(SSA) vs traditional serrated adenoma(TSA). American Journal of Surgical Pathology, 2008; 32(1): 21-29. 7. Hironori Aoki, Eiichiro Yamamoto, et al. Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer. Oncotarget, 2018; 9(4): 4707-4721. 8. Genetic/Familial High-Risk Assessment: Colorectal. NCCN Guidelines. Version 3. 2017.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma sample

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

• Pinghong Zhou, PhD

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Boqun Zhu, MD

CONTACT

+86 15800674292; zhu.boqun@zs-hospital.sh.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Endoscopy Center

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: February 4, 2019
• Study Start: October 26, 2018
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2020
• Last Updated: February 4, 2019

Record last verified: 2019-01

Locations

CN (1)