Hepatocellular CarcinomaNCT02036216
Circulating Cell-free DNA as a Predictive Biomarker for Hepatocelluar Carcinoma.
An observational study of Hepatocellular Carcinoma, run by Peking Union Medical College Hospital at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatocellular Carcinoma
- How many people
- 200 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2014to Mar 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Uncontrolled systemic disease Reject the surgical treatment Metastatic carcinoma Child-Pugh：child C
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Stanford Genome Technology Center
Stanford, California, 94304
Wenzhong Xiao, Dr, 650-725-1479, wzxiao@gmail.com
Wenzhong Xiao, Dr
China1 site, 1 recruiting
- Recruiting
Department of liver surgery; Peking Union Medical College Hospital；
Beijing, Beijing Municipality, 100730
Qining Fu, 861069156042, sky26pipi@gmail.com
Yilei Mao, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma；cell free tumor DNA; Mutation;
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
To collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC.
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.
Measured: three months
Secondary outcomes (4)
Investigate the value characteristic changes from the DNA samples.
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.
Measured: three months
Date analysis
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.
Measured: two months
Evaluate the sensitivity and specificity with these changes in HCC
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.
Measured: four months
Early diagnosis, treatment monitoring and prognosis evaluation.
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
Measured: twelve months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionJun 2014 (estimated)
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University
- Responsible party
- Sponsor
- Investigators
- Yilei Mao, MD, Principal investigator, PUMCH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02036216
- Sponsor's protocol ID
- CFD-J14
- Status last verified
- Jan 2014
- First submitted
- 7 Jan 2014
- Last updated
- 14 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Chen K, Zhang H, Zhang LN, Ju SQ, Qi J, Huang DF, Li F, Wei Q, Zhang J. Value of circulating cell-free DNA in diagnosis of hepatocelluar carcinoma. World J Gastroenterol. 2013 May 28;19(20):3143-9. doi: 10.3748/wjg.v19.i20.3143.
PubMed 23716996Gall TM, Frampton AE, Krell J, Habib NA, Castellano L, Stebbing J, Jiao LR. Cell-free DNA for the detection of pancreatic, liver and upper gastrointestinal cancers: has progress been made? Future Oncol. 2013 Dec;9(12):1861-9. doi: 10.2217/fon.13.152.
PubMed 24295416Shen P, Wang W, Chi AK, Fan Y, Davis RW, Scharfe C. Multiplex target capture with double-stranded DNA probes. Genome Med. 2013 May 29;5(5):50. doi: 10.1186/gm454. eCollection 2013.
PubMed 23718862
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detected the Valuable Characteristic Changes Both in Circulating Cell-free DNA and Primary Tumor in the Patients With Hepatocelluar Carcinoma.
- ClinicalTrials.gov ID
- NCT02036216
- Acronym / sponsor ID
- CFD-J14
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma；cell free tumor DNA; Mutation;
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Collaborators
- Stanford University
- Study start
- Jan 2014
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 14 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hepatocellular Carcinoma | – | –The mutation will be found in the DNA samples from the plasma and solid tumor tissues in the patients with HCC. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Uncontrolled systemic disease Reject the surgical treatment Metastatic carcinoma Child-Pugh：child C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
4 secondary outcomes
Investigate the value characteristic changes from the DNA samples.
Time frame: three months
Date analysis
Time frame: two months
Evaluate the sensitivity and specificity with these changes in HCC
Time frame: four months
Early diagnosis, treatment monitoring and prognosis evaluation.
Time frame: twelve months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2014.
- Background: PubMed 23716996Chen K, Zhang H, Zhang LN, Ju SQ, Qi J, Huang DF, Li F, Wei Q, Zhang J. Value of circulating cell-free DNA in diagnosis of hepatocelluar carcinoma. World J Gastroenterol. 2013 May 28;19(20):3143-9. doi: 10.3748/wjg.v19.i20.3143.
- Background: PubMed 24295416Gall TM, Frampton AE, Krell J, Habib NA, Castellano L, Stebbing J, Jiao LR. Cell-free DNA for the detection of pancreatic, liver and upper gastrointestinal cancers: has progress been made? Future Oncol. 2013 Dec;9(12):1861-9. doi: 10.2217/fon.13.152.
- Background: PubMed 23718862Shen P, Wang W, Chi AK, Fan Y, Davis RW, Scharfe C. Multiplex target capture with double-stranded DNA probes. Genome Med. 2013 May 29;5(5):50. doi: 10.1186/gm454. eCollection 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yilei Mao, MD principal investigator
PUMCH
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Peking Union Medical College Hospital at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yilei Mao, MD (13011079603, yileimao@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC. (time frame: three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02036216, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2014.