Liquid Biopsy in Hepatocellular Carcinoma (HCCGenePanel)

• ClinicalTrials.gov Identifier: NCT04111029
• Recruitment Status: Recruiting
• First Posted: October 1, 2019
• Last Update Posted: May 3, 2023
• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
• Information provided by (Responsible Party): Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh

Tracking Information

• First Submitted Date: September 26, 2019
• First Posted Date: October 1, 2019
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: January 16, 2020
• Estimated Primary Completion Date: December 16, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 28, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 28, 2019)

• Time to first recurrence (local or distant) diagnosed on follow up dynamic imaging. [ Time Frame: 90 days ]
• Mortality [ Time Frame: 90 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Liquid Biopsy in Hepatocellular Carcinoma
• Official Title: Assessment of Response to Locoregional Therapy Using Liquid Biopsy in Patients With Hepatocellular Carcinoma
• 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 Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Cell free DNA in Plasma will be stored

• Sampling Method: Non-Probability Sample

Study Population

A) All new consecutively diagnosed cases of Hepatocellular carcinoma (HCC) fulfilling the inclusion criteria, presenting to the Hepatology OPD and admitted to the LICU and/or wards for loco-regional therapy for the first time.

• All new cases of HCC diagnosed as per the AASLD 2018 guideline. HCC will be staged according to the Barcelona Clinic Liver Cancer (BCLC- Staging) system.
• The patients undergoing their first LRT (TACE/TARE/SBRT) with or without Sorafenib for HCC who are not eligible for resection/ liver transplantation or any other curative modality.
• Treatment allocation, as per the updated BCLC staging system and treatment strategy, which is also endorsed by the AASLD guidelines for the management of HCC

• Condition: Hepatic Carcinoma Malignant Primary Non-Resectable

Intervention

Diagnostic Test: Cell Free DNA

Pre and post procedure plasma cell free DNA will be assessed for response to locoregional therapy

Other Name: Liquid biopsy

Study Groups/Cohorts

Unresectable HCC undergoing locoregional therapy

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

Intervention: Diagnostic Test: Cell Free DNA

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 28, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2024
• Estimated Primary Completion Date: December 16, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Madhumita Premkumar, MD DM; 01722754777; drmadhumitap@gmail.com

Contact: Harman Dhaliwal, MSc; 0117087003409

• Listed Location Countries: India

Administrative Information

• NCT Number: NCT04111029
• Other Study ID Numbers: INT/HEP/1078
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh
• Original Responsible Party: Same as current
• Current Study Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Radhika Srinivasan, MD PhD; Post Graduate Institute of Medical Education and Research, Chandigarh

• PRS Account: PGIMER
• Verification Date: April 2023