Clinical trial NCT03939975: Anti-PD-1therapy Combined With Thermal Ablation for Advanced HCC
Official title: A Prospective Study of Anti-PD-1 Inhibitors Therapy in Combination With Incomplete Thermal Ablation in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Hepatocellular carcinoma
Immunotherapy
Nivolumab
Pembrolizumab
Radiofrequency Ablation
Microwave ablation
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-05-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study subjects were those who with advanced HCC that progressed on first-line sorafenib and treated with anti-PD-1 therapy in combination with incomplete thermal ablation.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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.

Primary outcomes:
measure: Adverse events
timeFrame: 6-8 weeks
measure: Response
timeFrame: 6-8 weeks
Secondary outcomes:
measure: Time to tumor progression
timeFrame: 3-4 months
measure: Progression-free survival
timeFrame: 3-4 months
measure: Overall survival
timeFrame: 3-4 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ming Zhao, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lyu N, Kong Y, Li X, Mu L, Deng H, Chen H, He M, Lai J, Li J, Tang H, Lin Y, Zhao M. Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study. Front Oncol. 2020 Oct 9;10:580241. doi: 10.3389/fonc.2020.580241. eCollection 2020.