Liquid Biopsy in Hepatocellular Carcinoma

Recruiting

• Conditions: Hepatic Carcinoma Malignant Primary Non-Resectable
• Interventions: Diagnostic Test: Cell Free DNA

• Registration Number: NCT04111029
• Lead Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Brief Summary

Circulating tumor DNA (ctDNA) carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Hepatocellular carcinoma (HCC) specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Use of 'liquid biopsy' by assessing circulating cell free DNA enables the clinician to offer targeted immunotherapy or signaling pathway inhibitors. It also offers a model to prove response to locoregional or immunotherapy therapy and predict tumor recurrence non-invasively.

Detailed Description

Novelty:

Mutation analysis may not only help identify cancer drivers, but they can also provide useful data to predict response to other treatment modalities such as immunotherapies, particularly immune checkpoint blockade. There is published data on liquid biopsy in India from oncology in the field of pulmonary and renal cancers, but these studies have not been done in cirrhosis or in HCC patients.

Objectives In this project we hope to develop a biomarker panel which helps us prognosticate patients and tailor targeted therapy as per their genetic mutation landscape. The treatment options for advanced HCC are limited, and tissue biopsy is not routinely performed.

Methods In this pilot project, we will analyze 30 patients with unresectable hepatocellular carcinoma, ineligible for liver transplantation, who will undergo locoregional therapy in the form of transarterial chemoembolization (TACE) or radioembolization (TARE) for tissue diagnosis of tumor tissue DNA and circulating tumor DNA. We will design personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing will be performed using cell-free DNA and paired primary tumor tissue DNA in order to create a non-invasive liquid biopsy for diagnosis and prognostication of HCC.

Study Timeline

• Study First Submitted: 2019-09-26
• Study First Submitted QC: 2019-09-28
• Study First Posted: 2019-10-01
• Study Start: 2020-01-16
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-28
• Last Update Posted: 2023-05-03
• Primary Completion: 2023-12-16
• Study Completion: 2024-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Hepatocellular carcinoma BCLC stages B and C of all aetiology, unresectable
• Age 18-70 years of either sex

Exclusion Criteria

• Contemplating Hepatic resection or OLT
• Refractory ascites
• Severe Coagulation disorders prior to the procedure (PTI <70% and Platelet count < 80,000/mm3)
• Hepato-Renal syndrome
• Chronic Kidney Disease
• Acute decompensation like Hepatic encephalopathy and variceal bleeding
• Any known malignancy other than HCC
• Life expectancy < 6 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Unresectable HCC undergoing locoregional therapy	Cell Free DNA	Patients with unresectable HCC who have no curative option like tumour ablation, resection or transplantation and are being taken for locoregional therapy will be recruited

Primary Outcome Measures

Name	Time	Method
Serial Quantification of ctDNA in plasma samples by means of real-time PCR post treatment	90 days
Comparison of exome sequencing of primary tumor tissue and cell-free DNA from plasma samples	0, 90 days

Secondary Outcome Measures

Name	Time	Method
Time to first recurrence (local or distant) diagnosed on follow up dynamic imaging.	90 days
Mortality	90 days

Trial Locations

Locations (1)

Postgraduate Institute of Medical Education and Research; 🇮🇳 Chandigarh, Choose Any State/Province, India