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Trial Title:
A Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma
NCT ID:
NCT05752890
Condition:
Hepatocellular Carcinoma
Hepatitis b Virus
Radiotherapy
Biomarker
Conditions: Official terms:
Hepatitis B
Carcinoma
Carcinoma, Hepatocellular
Hepatitis
Conditions: Keywords:
Hepatocellular Carcinoma
Hepatitis b Virus
Radiotherapy
Chimera DNA
Biomarker
Study type:
Observational [Patient Registry]
Overall status:
Not yet recruiting
Study design:
Time perspective:
Other
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 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.
Criteria for eligibility:
Study pop:
we have been prospectively collecting plasma samples from HBV-related HCC patients
before/after RT, at 1, 4, 7 months, and at recurrence/metastasis.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. Patients diagnosed with HCC by dynamic image criteria and/or biopsy
2. HBsAg (+)
3. Child-Turcotte-Pugh (CTP) class A-B liver function
4. Radiotherapy to liver tumor as the main treatment
Exclusion Criteria:
1. Child-Turcotte-Pugh (CTP) class C liver functiECOG performance status score >2
2. Has had prior radiotherapy to the proposed treatment field.
3. < 18 years old
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
March 1, 2023
Completion date:
January 31, 2031
Lead sponsor:
Agency:
National Taiwan University Hospital
Agency class:
Other
Source:
National Taiwan University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05752890
