Circulating Cell-free DNA as a Predictive Biomarker for Hepatocelluar Carcinoma.

January 12, 2014 updated by: Peking Union Medical College Hospital

Detected the Valuable Characteristic Changes Both in Circulating Cell-free DNA and Primary Tumor in the Patients With Hepatocelluar Carcinoma.

Circulating free cell DNA (cfDNA) is extracellular fragmentation of nucleic acids that occurs both in plasma and serum. This kind of DNA which derived from the apoptotic/necrotic cells or the lysis of circulating tumor cells (CTCs) can be detectedin the patients with a variety of diseases. Emerging evidence suggests that cfDNA from patients exhibits characteristicchanges of tumors, suchas mutations, insertions/deletions, methylations,microsatellite aberrations, and copy number variations, etc. All of these reveal a visible difference between the benign conditions, and thus may be useful in the diagnosis of cancer, identification of targeted therapy, monitor responses to treatments, and early detection of relapse. The purpose for this study is to explore these characteristic changes in the patients withhepatocellular carcinoma (HCC) and expect to guide targeted therapy and identify non-invasive biomarkers of cancer diagnosis and prognosis which can be easily isolated from the circulation.

Study Overview

Status

Unknown

Conditions

Detailed Description

In cancer, cfDNA can be detected a higher concentration in the circulation because of the necrosis of neoplasm cells with the rapid enlargement and relatively shortage of blood supply. So, identifying tumor-specific genetic and epigenetic changes in cfDNA on this status, such as gene mutations, deletions, methylation alterations and microsatellite alterations, may be more specific for us to diagnose the neoplasms in early phase. This phenomenon also appears in the patients with hepatocellular carcinoma (HCC). Studies have shown that cfDNA level is associated with intrahepatic and extrahepatic metastasis in HCC patients and examined some cfDNAcharacteristic changes, such as p161NK4A, RTL, RASSF1A, LINE-1 and GSTP1. Thus is useful for us to explore the specific cfDNA in HCC. For a high sensitivity and specificity detection, we will use technologiesdeveloped at Stanford Genome Technology Centerto find more characteristic gene mutations, methylation alterations or other changes (3). In this study, we willinvestigate thesecharacteristic changesin cfDNA and primary tumor lesions.

Study arrangement:

Collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC.

Detect the DNA sequence from the samples of plasma, blood cells and solid tumor tissues.

Identify cancer specific variations in cfDNA and primary tumor lesions. Date analysis and investigate these characteristic changes. Evaluate the application in early diagnosis, treatment monitoring and prognosis for HCC.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Department of liver surgery; Peking Union Medical College Hospital；
        • Contact:
        • Sub-Investigator:
          • Haifeng Xu, Dr
        • Sub-Investigator:
          • Wenjun Liao, Dr
  • United States
    • California
      • Stanford, California, United States, 94304
        • Recruiting
        • Stanford Genome Technology Center
        • Contact:
        • Principal Investigator:
          • Wenzhong Xiao, Dr
        • Sub-Investigator:
          • Peidong Shen, Dr
        • Sub-Investigator:
          • Weihong Xu, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The HCC patients who will receive the surgical treatment in Peking Union Medical College Hospital from Jan of 2014 till the end of this study.

Description

Inclusion Criteria:

Age≥18years and ≤80 years; Histologically and cytologically proven Hepatocellular carcinoma Child-Pugh：child A-B Adequate hematological, renal, cardiac and pulmonary functions Tumor in any segment of liver

Exclusion Criteria:

Uncontrolled systemic disease Reject the surgical treatment Metastatic carcinoma Child-Pugh：child C

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Hepatocellular Carcinoma
The mutation will be found in the DNA samples from the plasma and solid tumor tissues in the patients with HCC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC.
Time Frame: three months
In the first three months in this study, we will collect 5 samples from the plasma, blood cells and primary tumor lesions in the patients with HCC in three stages including preoperative, postoperative (2 weeks) and postoperative (1 month). It is better for us to find the characteristic changes when we make a detailed comparison between the samples in these period. These samples include 5ml plasma, 2ml blood cells without plasma and at least 10mg solid tumor tissues.
three months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Investigate the value characteristic changes from the DNA samples.
Time Frame: three months
We will prepare the DNA samples from the plasma, blood cells and primary tumor lesions in the patients with HCC in Stanford Genome Technology Center. And then, we will finish DNA sequence in both of them. The DNA sequence which detect from the blood cells will be a normal standard, and thus will be compared with the DNA sequence detect in the samples of plasma and tumor tissues. In this way, we expect to find the common mutations in cfDNA and primary tumor lesions.
three months
Date analysis
Time Frame: two months
Date analysis will help us to find the changes which have the highest probability in DNA sequence. After that, we will screen these characteristic changes and confirm the sensitive and special mutations which can help us to diagnose the HCC in early phase.
two months
Evaluate the sensitivity and specificity with these changes in HCC
Time Frame: four months
After we find these valuable characteristic changes in HCC, 50 samples will be detected within these changes. On the basis of the deepen date analysis, we will evaluate the sensitivity and specificity with these changes in HCC.
four months
Early diagnosis, treatment monitoring and prognosis evaluation.
Time Frame: twelve months
After we complete the evaluation and determine which genetic changes can be used, we will choose 100 patients with HCC and 50 patients who have accepted the surgery treatment in this trial phase. The first 100 patients will be detected these changes before the operation. After that, we expect to establish an evaluation system for early diagnosis in HCC. The postoperative patients will accept the cfDNA detection in the same way with the purpose of estimating the recurrence of the tumor
twelve months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (ANTICIPATED)

June 1, 2014

Study Completion (ANTICIPATED)

March 1, 2016

Study Registration Dates

First Submitted

January 7, 2014

First Submitted That Met QC Criteria

January 12, 2014

First Posted (ESTIMATE)

January 14, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

January 14, 2014

Last Update Submitted That Met QC Criteria

January 12, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFD-J14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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