Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03923335
Recruitment Status : Not yet recruiting
First Posted : April 22, 2019
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
Sixth Affiliated Hospital, Sun Yat-sen University

Brief Summary:
This study aims to evaluate the predictive value of a four-gene methylation assay called Guangzhou Panel in early-stage colorectal cancer. Patients will be divided into two groups: high risk group and low risk group. The primary endpoint is 5 year disease free survival (DFS).

Condition or disease Intervention/treatment
Colorectal Neoplasms Other: DNA methylation detection

Detailed Description:

The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system.

In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287).

Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel.

The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 287 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer
Estimated Study Start Date : April 30, 2019
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
high-risk group
patients with any of the four genes hypermethylated
Other: DNA methylation detection
detecting the methylation status of colorectal cancer specimen

low-risk group
patients with none of the four genes hypermethylated
Other: DNA methylation detection
detecting the methylation status of colorectal cancer specimen




Primary Outcome Measures :
  1. disease free survival [ Time Frame: From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years ]
    the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer


Biospecimen Retention:   Samples With DNA
tissue specimen from colorectal cancer patients who underwent radical resection


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients that had pathologically verified stage I-II CRC and underwent surgical resection in Sixth Affiliate Hospital of Sun Yat-sen University
Criteria

Inclusion Criteria:

  1. TNM stage I-II (T1-4N0M0) colorectal cancer cases
  2. receive radical surgical resection
  3. have completed data of tumor location, histological type, behavioral characteristics or TNM staging
  4. have tumor specimens and either a valid microsatellite instability (MSI) or immuno-histochemistry (IHC) data
  5. have valid V-raf murine sarcoma viral oncogene homolog B1 (BRAF), kirsten rat sarcoma viral oncogene (KRAS), CpG island methylator phenotype (CIMP) results
  6. have at least 4 years of follow-up
  7. have valid time to local recurrence/metastasis in follow-up
  8. have clinical/treatment record data and valid preoperative status of intestinal obstruction or perforation (IOP), counts of lymph node removed in surgical resection.

Exclusion Criteria:

  1. have had a previous diagnosis of any cancer or presence of any tumor other than the CRC
  2. have had inflammatory bowel disease
  3. have had hereditary colorectal cancer syndromes, including Familial adenomatous polyposis, mutyh (MYH)-associated polyposis, Peutz-Jeghers syndrome, Juvenile polyposis coli, phosphate and tension homology deleted on chromosome ten (PTEN) tumor-hamartoma syndromes, Lynch Syndrome, and Familial Colorectal Cancer Type X.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03923335


Contacts
Layout table for location contacts
Contact: Yanxin Luo, MD,PhD +86-13826190263 luoyx25@mail.sysu.edu.cn
Contact: Du Cai, MD +86-18819481550 caid6@mail2.sysu.edu.cn

Locations
Layout table for location information
China, Guangdong
The Sixth Affiliate Hospital of Sun Yat-Sen University Not yet recruiting
Guangzhou, Guangdong, China, 510655
Contact: Yanxin Luo, PhD,MD    +86-13826190263    luoyx25@mail.sysu.edu.cn   
Contact: Du Cai, MD    +86-18819481550    caid6@mail2.sysu.edu.cn   
Sponsors and Collaborators
Sixth Affiliated Hospital, Sun Yat-sen University
Investigators
Layout table for investigator information
Principal Investigator: Yanxin Luo, MD,PhD The Sixth Affiliated Hospital, Sun Yat-sen University

Publications:

Layout table for additonal information
Responsible Party: Sixth Affiliated Hospital, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT03923335     History of Changes
Other Study ID Numbers: Luo-20190326
First Posted: April 22, 2019    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Our DNA methylation panel is applying for patent protection, therefore we plan to keep the data private for the time being.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sixth Affiliated Hospital, Sun Yat-sen University:
colorectal cancer
prognostic biomarkers
DNA Methylation
gene panel
recurrence
disease free survival

Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Recurrence
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Disease Attributes
Pathologic Processes