Hepatocellular CarcinomaNCT05752890
A Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma
An observational study of Hepatocellular Carcinoma and Hepatitis b Virus, run by National Taiwan University Hospital.
Trial summary
The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Hepatitis b Virus, Radiotherapy
- How many people
- 95 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2023to 31 Jan 2031
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: we have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis.
Who may be able to join
- Patients diagnosed with HCC by dynamic image criteria and/or biopsy
- HBsAg (+)
- Child-Turcotte-Pugh (CTP) class A-B liver function
- Radiotherapy to liver tumor as the main treatment
Who cannot join
- Child-Turcotte-Pugh (CTP) class C liver functiECOG performance status score >2
- Has had prior radiotherapy to the proposed treatment field.
- < 18 years old
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Developing a Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma Treated With Radiotherapy: Personalized Cell-free Virus-host Chimera DNA
The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.
The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.
Read the detailed description
Residual tumors and early recurrence/metastasis after radiotherapy (RT) compromise the patient survival with hepatocellular carcinoma (HCC). Timely detecting residual/recurrence/metastasis and the clonality is required to implement salvage therapies properly. The major unmet needs of radiotherapy to HCC are the difficulties in early evaluating response by images and timely detection of intrahepatic recurrence and extrahepatic metastasis. Thus, an accurate and personalized biomarker for response prediction and disease monitoring is demanded. Cell-free tumor-specific DNA (ctDNA) has garnered attention as a promising biomarker in cancer patients. However, in HCC, the detection rate is low (9-21.2%), mainly due to the limited prevalence of traditional somatic mutations and the difficult separation of ctDNA fragments from normal cells. The investigators aim to develop a novel ctDNA, the virus-host chimera DNA (vh-DNA), as a biomarker for hepatitis B virus (HBV)-related HCC patients undergoing RT. HBV vh-DNA presents in ~90% of HBV-related HCC patients and can be differentiated from DNA released from the normal cells through enrichment by capturing with HBV probes. vh-DNA might be advantageous to the traditional somatic mutation type of ctDNA. The investigators hypothesize that HBV vh-DNA could accurately diagnose residual tumor by 6-12 months earlier than contemporary images and predict early recurrence/metastatsis, thus allows early intervention of salvage therapies.
The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.
The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.
- Conditions
- Hepatocellular Carcinoma, Hepatitis b Virus, Radiotherapy, Biomarker
- Keywords
- Hepatocellular Carcinoma, Hepatitis b Virus, Radiotherapy, Chimera DNA, Biomarker
- Medical subject headings
- Carcinoma, Hepatocellular, Hepatitis B
What is being measured
The primary outcome is the main question the study is designed to answer.
To retrospectively analyze the Capture-NGS analysis from HBV-related HCC patients
Capture-NGS analysis and identification of HBV-human junction between pre- and post- RT
Measured: 2031/01/01
To retrospectively analyze the Vh-DNA specific PCR from HBV-related HCC patients
Vh-DNA specific PCR between pre- and post- RT
Measured: 2031/01/01
To retrospectively analyze the serial changes of serum vh-DNA copies of same junction clone from HBV-related HCC patients
Treatment response between pre- and post- RT
Measured: 2031/01/01
To retrospectively analyze the serial changes of survival of same junction clone from HBV-related HCC patients
Survival between pre- and post- RT
Measured: 2031/01/01
To prospectively test the concordance of vh-DNA copies between serum and plasma samples
Calculate the percentage of identical vhDNA sets between the simultaneously collected serum and plasma samples in the same patients
Measured: 2031/01/01
To prospectively analyze the serial changes of plasma vh-DNA copies of same junction clone are associated with treatment response
Treatment response will be determined as the best response in serial image follow-ups up to 6 months after completion of RT. Responses will be classified as completion response, partial response, stable disease, and progressive disease by the definition of mRECIST.
Measured: 2031/01/01
To prospectively analyze the serial changes of plasma vh-DNA copies of same junction clone are associated with overall survival
It will be calculated from the last fraction of radiotherapy until death from any cause of last follow-up.
Measured: 2031/01/01
To distinguish the clonality of recurrent HCC as the original or a de novo one for post-radiotherapy patterns of failure
Detected tumor-specific vh-DNA in the plasma collected at the time of recurrence/metastasis to determine its clonality.
Measured: 2031/01/01
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2023
- Study start1 Mar 2023 (estimated)
- Primary completion31 Jan 2031 (estimated)
- Study completion31 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University 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
- Cohort
- Time perspective
- Other
- Enrolment
- 95 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chia-Hsien Cheng, Principal investigator, Employee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05752890
- Sponsor's protocol ID
- 202212021RINB
- Status last verified
- Jan 2023
- First submitted
- 30 Jan 2023
- Last updated
- 3 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing a Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma Treated With Radiotherapy: Personalized Cell-free Virus-host Chimera DNA
- ClinicalTrials.gov ID
- NCT05752890
- Acronym / sponsor ID
- 202212021RINB
- Conditions
- Hepatocellular Carcinoma, Hepatitis b Virus, Radiotherapy, Biomarker
- Keywords
- Hepatocellular Carcinoma, Hepatitis b Virus, Radiotherapy, Chimera DNA, Biomarker
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 95 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2023 (estimated)
- Primary completion
- 31 Jan 2031 (estimated)
- Study completion
- 31 Jan 2031 (estimated)
- First posted
- 3 Mar 2023 (actual)
- 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.
The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.
The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.
Detailed description
Residual tumors and early recurrence/metastasis after radiotherapy (RT) compromise the patient survival with hepatocellular carcinoma (HCC). Timely detecting residual/recurrence/metastasis and the clonality is required to implement salvage therapies properly. The major unmet needs of radiotherapy to HCC are the difficulties in early evaluating response by images and timely detection of intrahepatic recurrence and extrahepatic metastasis. Thus, an accurate and personalized biomarker for response prediction and disease monitoring is demanded. Cell-free tumor-specific DNA (ctDNA) has garnered attention as a promising biomarker in cancer patients. However, in HCC, the detection rate is low (9-21.2%), mainly due to the limited prevalence of traditional somatic mutations and the difficult separation of ctDNA fragments from normal cells. The investigators aim to develop a novel ctDNA, the virus-host chimera DNA (vh-DNA), as a biomarker for hepatitis B virus (HBV)-related HCC patients undergoing RT. HBV vh-DNA presents in ~90% of HBV-related HCC patients and can be differentiated from DNA released from the normal cells through enrichment by capturing with HBV probes. vh-DNA might be advantageous to the traditional somatic mutation type of ctDNA. The investigators hypothesize that HBV vh-DNA could accurately diagnose residual tumor by 6-12 months earlier than contemporary images and predict early recurrence/metastatsis, thus allows early intervention of salvage therapies.
The investigators will first use our previously collected serum samples and surgical/biopsied tissues from HBV-related HCC patients undergoing radiotherapy. The consistency of junctional clones by Capture NGS needs to be tested between both pre- and post-RT serums, and serial changes in copy numbers of vh-DNA by ddPCR are quantified in the representative cases. The same junction clones from pre-post-RT serums and surgical tissues will be confirmed and the copy number changes of vh-DNA be correlated with RT response and disease-control status.
The investigators plan to identify HBV integrations by Capture NGS and quantify the specific vh-DNA by ddPCR as personalized biomarkers from the same-patient serum samples. The investigators will further correlate clinical response and recurrence/metastasis with serial changes of vh-DNA copy numbers. The investigators have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis. The investigators plan to confirm the viable role of pre-/post-RT changes of plasma vh-DNA copies of the same junction clone in post-RT response and prognosis. Moreover, The investigators will explore the recurrent/metastatic tumors arising from the original or a de novo one by identifying their clonality with HBV integration patterns. The true value of this novel HBV chimera vh-DNA will be revealed. The results will also support the consolidative use of personalized vh-DNA for earlier evaluating treatment response after RT, for post-RT disease monitoring, and for differentiating clonality at recurrence to design future clinical trial on combinational treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 3 Months
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- we have been prospectively collecting plasma samples from HBV-related HCC patients before/after RT, at 1, 4, 7 months, and at recurrence/metastasis.
Key inclusion criteria (4 listed)
- Patients diagnosed with HCC by dynamic image criteria and/or biopsy
- HBsAg (+)
- Child-Turcotte-Pugh (CTP) class A-B liver function
- Radiotherapy to liver tumor as the main treatment
Key exclusion criteria (3 listed)
- Child-Turcotte-Pugh (CTP) class C liver functiECOG performance status score >2
- Has had prior radiotherapy to the proposed treatment field.
- < 18 years old
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 retrospectively analyze the Capture-NGS analysis from HBV-related HCC patients
Time frame: 2031/01/01
Capture-NGS analysis and identification of HBV-human junction between pre- and post- RT
To retrospectively analyze the Vh-DNA specific PCR from HBV-related HCC patients
Time frame: 2031/01/01
Vh-DNA specific PCR between pre- and post- RT
To retrospectively analyze the serial changes of serum vh-DNA copies of same junction clone from HBV-related HCC patients
Time frame: 2031/01/01
Treatment response between pre- and post- RT
To retrospectively analyze the serial changes of survival of same junction clone from HBV-related HCC patients
Time frame: 2031/01/01
Survival between pre- and post- RT
To prospectively test the concordance of vh-DNA copies between serum and plasma samples
Time frame: 2031/01/01
Calculate the percentage of identical vhDNA sets between the simultaneously collected serum and plasma samples in the same patients
To prospectively analyze the serial changes of plasma vh-DNA copies of same junction clone are associated with treatment response
Time frame: 2031/01/01
Treatment response will be determined as the best response in serial image follow-ups up to 6 months after completion of RT. Responses will be classified as completion response, partial response, stable disease, and progressive disease by the definition of mRECIST.
To prospectively analyze the serial changes of plasma vh-DNA copies of same junction clone are associated with overall survival
Time frame: 2031/01/01
It will be calculated from the last fraction of radiotherapy until death from any cause of last follow-up.
To distinguish the clonality of recurrent HCC as the original or a de novo one for post-radiotherapy patterns of failure
Time frame: 2031/01/01
Detected tumor-specific vh-DNA in the plasma collected at the time of recurrence/metastasis to determine its clonality.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
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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.
Chia-Hsien Cheng principal investigator
Employee
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma and Hepatitis b Virus, run by National Taiwan University Hospital.
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 4 inclusion and 3 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: opening soon, as of the sponsor's last update on 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chia-Hsien Cheng (886-223123456 ext. 67141, jasoncheng@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To retrospectively analyze the Capture-NGS analysis from HBV-related HCC patients (time frame: 2031/01/01). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Mar 2023.