Clinical trial NCT03737591: The Implication of Plasma ctDNA Methylation Haplotypes in Detecting Colorectal Cancer and Adenomas
Official title: The Implication of Plasma Circulating Tumor DNA Methylation Haplotypes in Detecting Colorectal Cancer and Adenomas: a Multicenter, Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Adenoma
Keywords: Colorectal Cancer
Adenomas
ctDNA Methylation Haplotypes
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Southern Medical University, China
First posted: 2018-11-09
Enrollment: 1138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy individuals and patients with stage I-IV colorectal cancer or adenomas must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent.

Brief summary: This is a multicenter, clinical study. This study is to evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer, adenoma and the specificity in healthy individuals.

Detailed description: Colorectal cancer (CRC) is the third most common cancer worldwide, the second deadliest cancer in the United States. DNA methylation is a commonly used biomarker for non-invasive CRC detection in plasma. The low sensitivity of blood-based tests is due to several limitations of detecting ctDNA in early-stage cancer. We developed and validated a high-throughput methylation-based blood test highly sensitive for colorectal cancer and precancerous lesions. This previously established colorectal tumor-specific plasma ctDNA methylation markers (diagnostic model established by next-generation sequencing of gene loci methylation) had a high sensitivity in CRC patients and a high specificity in healthy individuals in a large retrospective sample study. This prospective, multicenter, clinical study is to further evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer, adenoma and the specificity in healthy individuals.

Eligibility criteria: Inclusion Criteria:

Healthy Individuals:

* Written informed consent must be obtained from healthy individuals to comply with the requirements of the study.
* Healthy individuals who received colonoscopy.

Patients with Colorectal Cancer or Adenomas:

* Male or female ≥ 18 years of age on the day of signing informed consent.
* Patients need to receive surgical resection or endoscopic resection.
* Patients must have histologically confirmed stage I-IV colorectal cancer or adenomas
* Patients must have a performance status of ≤1 on the ECOG Performance Scale.
* Written informed consent must be obtained from patient or patient's legal representative and ability for patient to comply with the requirements of the study.

Exclusion Criteria:

* Patients received adjuvant treatment prior to the surgical resection.
* Patients received blood transfusion two weeks before or during the surgical resection.
* Patients with unresected advanced colorectal adenoma.
* Patients who are positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C.
* Patients who are pregnant.
* Patients who are alcoholic or drug abusers.
* Patients with a history or current evidence of any condition or abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Investigator.

Primary outcomes:
measure: Sensitivity
timeFrame: 2 years
measure: Specificity
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
References:
citation: Mo S, Dai W, Wang H, Lan X, Ma C, Su Z, Xiang W, Han L, Luo W, Zhang L, Wang R, Zhang Y, Zhang W, Yang L, Lu R, Guo L, Zheng Y, Huang M, Xu Y, Liang L, Cai S, Cai G. Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study. EClinicalMedicine. 2022 Nov 3;55:101717. doi: 10.1016/j.eclinm.2022.101717. eCollection 2023 Jan.