A Novel Biomarker for Response and Prognosis of HBV-related Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05752890
• Other study ID #: 202212021RINB
• Status: Not yet recruiting
• Start date: March 1, 2023
• Est. completion date: January 31, 2031

Study information

• Verified date: January 2023
• Source: National Taiwan University Hospital
• Contact: Chia-Hsien Cheng
• Phone: 886-223123456
• Email: jasoncheng[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 95
• Est. completion date: January 31, 2031
• Est. primary completion date: January 31, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Biomarker
• Carcinoma
• Carcinoma, Hepatocellular
• Hepatitis
• Hepatitis B
• Hepatitis b Virus
• Hepatocellular Carcinoma
• Radiotherapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2031/01/01
Primary	To retrospectively analyze the Vh-DNA specific PCR from HBV-related HCC patients	Vh-DNA specific PCR between pre- and post- RT	2031/01/01
Primary	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	2031/01/01
Primary	To retrospectively analyze the serial changes of survival of same junction clone from HBV-related HCC patients	Survival between pre- and post- RT	2031/01/01
Primary	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	2031/01/01
Primary	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.	2031/01/01
Primary	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.	2031/01/01
Primary	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.	2031/01/01