Analysis of cfDNA in Patients With Hepatocarcinoma and Treated by Sorafenib or Regorafenib — HELP  

Hepatocarcinoma Clinical Trial

Official title: A Sorafenib-Regorafenib Sequence Treatment Monitoring Study Using Liquid Biopsy

Status Terminated

Clinical Trial Summary

The aim of this trial is to investigate whether quantitative analysis of the total concentration of circulating free deoxyribonucleic acid (cfDNA) and of the cfDNA integrity index (DII) (Intplex®) may reflect hepatocellular carcinoma (HCC) tumor dynamics or response for patients treated by Sorafenib or Regorafenib and if it could be used as a tool for patient management under targeted therapy.

Clinical Trial Description

Circulating free deoxyribonucleic acid (cfDNA) is increasingly used in oncology with the aiml of early diagnosis of the disease, its therapeutic management and monitoring the evolution of the disease. Numerous publications have shown that the cfDNA concentration is correlated with the pathology of cancer. Larger amounts of cfDNA are detected in metastatic patients or patients with advanced cancer. However, the cfDNA concentrations have not yet shown their clinical interest mainly because of the variations in the same individual during the effort or the moment of collection of the blood sample. The concept of the integrity of cfDNA has also been studied as a biomarker in oncology and seems to show an interesting clinical value. The cfDNA is essentially released by cell apoptosis generating 170 bp fragments, corresponding to the size of a nucleosome. Many studies have shown that the integrity of cfDNA increases with the pathology of cancer. Thus, tumor-derived cfDNA is more fragmented than healthy cells with fragments smaller than the size nucleosome.

To date, no predictive biomarker is available for the management of treatment with Sorafenib which is a targeted therapy with a marketing authorization in first-line treatment of HCC (hepatocellular carcinoma) or second line with Regorafenib, treatment having shown a benefit positive on overall survival in the Resorce study. AFP (alpha-foetoprotein) is the only serum marker available with an inconstant increase in patients with HCC in fact only 30 to 40% of patients have abnormal values. In liver cancer, Ono et al showed that serum cfDNA is positively correlated with a larger tumor size.

This study shows that the rate of tumor cfDNA reflects the progression of the disease. Jiang et al showed that cfDNA derived from HCC is more fragmented than that derived from healthy cells, with fragments smaller than the size nucleosome.

These data demonstrate the potential utility of cfDNA amount and integrity as a biomarker for individualized management of hepatocellular carcinoma.

This new marker is expected to be an effective tool to overcome the lack of specificity of the AFP (alpha foetoprotein) assay in this pathology.

The investigator's team developed an Intplex® test that showed significant discrimination between healthy individuals and cancer patients.

The aim of this trial is to investigate whether quantitative analysis of the total concentration of cfDNA and of the cfDNA integrity index (DII) (Intplex®) may reflect HCC tumor dynamics or response for patients treated by Sorafenib or Regorafenib and if it could be used as a tool for patient management under targeted therapy. ;

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocarcinoma

• NCT number: NCT03956940
• Study type: Interventional
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Status: Terminated
• Phase: N/A
• Start date: October 4, 2019
• Completion date: December 31, 2021