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Currently, you can access the following clinical trials being conducted worldwide:
Clinicaltrials.gov identifier NCT03939975
Recruitment Status Completed
First Posted May 7, 2019
Last update posted August 19, 2019
The inhibition of programmed cell death protein 1 (PD-1) has shown promising antitumor activity in advanced hepatocellular carcinoma (HCC). Unfortunately, less than 20% of HCC have response. The effect of PD-1 blockade and incomplete thermal ablation in patients with advanced HCC is not yet clearly understood. This study aimed to analyze outcomes of advanced HCC treated with anti PD-1 inhibitors in combination with incomplete thermal ablation.
Hepatocellular carcinoma (HCC) is ranked as the third leading cause of cancer death both worldwide and in the China. In the past decade, survivals of patients with advanced HCC or those who have progressed diseases following locoregional treatments can be increased with the multi-kinase inhibitor sorafenib, the first evidence identified drug for HCC. Recent clinical trials further verified some novel tyrosine kinase inhibitors such as regorafenib and cabozantinib, and two programmed cell death protein-1 (PD-1) immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab, as useful therapies in second line setting following sorafenib. Advances in programmed cell death protein 1 (PD-1) blockade have shown an ORR of 15-17% and median survival time of 12.9-15.0 months among patients with advanced HCC. Of these, nivolumab and pembrolizumab have been accelerated approved as second-line treatment of advanced HCC. Notably, patients who have tumor responses maintain long-lasting disease control for 9.9-17months and still a large proportion of patients (81-83%) do not respond to mono PD-1 blockade, which emphasizing the need to explore strategies to increase the efficacy of immunotherapy. An approach to expanding the benefit of ICIs may involve combinations with locoregional therapy like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), such treatments have been shown to boost tumor-specific T-cell response through release of TAAs from HCC cells. The intent-to-treat population of this study was a subset of patients receiving ongoing ICIs therapy for advanced HCC and is with stable disease or atypical responses in different lesions of the same individuals.
|Experimental: Study arm
Patients with stable diseases or atypical progression to ICIs monotherapy would be additionally treated with incomplete thermal ablation along with ICIs therapy; and for those who with no lesions eligible for Incomplete ablation, ICIs would be given solely. Others with complete or partial responses would keep on going with mono-ICIs therapy.
Drug: pembrolizumab or nivolumab or JS001
ICIs therapy of nivolumab (3 mg/kg, per 2 weeks) or pembrolizumab (2 mg/kg, per 3 weeks) or JS001 (240mg, per 3 weeks) was performed until the off-treatment criteria were met. For participants with stable disease or atypical progression to ICIs therapy, thermal ablation of radiofrequency ablation or microwave ablation was performed addtionally.
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Eligible patients had pathological diagnosis of HCC by either surgical resection tissue or
core needle biopsy; and had advanced stage of disease that is refractory to or is with
unacceptable toxicity of sorafenib. Other eligibility criteria included: Child-Pugh A or B7
classification; Eastern Cooperative Oncology Group-performance status score 0-2; adequate
bone marrow (leukocyte count >3.0 ×109/L, hemoglobin >8.0 g/L, and platelet count >60
×109/L), liver (alanine aminotransferase and aspartate aminotransferase <200 IU/mL), renal (creatinine <1.5 times the upper limit of the normal range) and coagulation (international normalized ratio <2.3) function. Exclusion Criteria: - Exclusion criteria included a history of treatment with immune checkpoint inhibitors, allergies to immunetherapeutics, systemic immunosuppressive therapy, and ongoing or active infection, or an active autoimmune disease.
Sun Yat-sen University Cancer Center
Sun Yat-sen University
Principal Investigator: Ming Zhao, MD, Ph.D Sun Yat-sen University