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Anti-PD-1therapy Combined With Thermal Ablation for Advanced HCC

  • Clinicaltrials.gov identifier

    NCT03939975

  • Recruitment Status

    Completed

  • First Posted

    May 7, 2019

  • Last update posted

    August 19, 2019

Study Description

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.

  • Condition or Disease:Carcinoma, Hepatocellular
  • Intervention/Treatment: Drug: pembrolizumab or nivolumab or JS001
  • Phase: Phase 2

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.

Study Design

  • Study Type: Interventional
  • Actual Enrollment: 50 participants
  • Intervention Model: Single Group Assignment
  • 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.
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Prospective Study of Anti-PD-1 Inhibitors Therapy in Combination With Incomplete Thermal Ablation in Patients With Advanced Hepatocellular Carcinoma
  • Actual Study Start Date: June 2019
  • Actual Primary Completion Date: July 2019
  • Actual Study Completion Date: July 2019

Arms and interventions

Arm Intervention/treatment
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.

Outcome Measures

  • Primary Outcome Measures: 1. Adverse events [ Time Frame: 6-8 weeks ]
    Safety evaluation was done continuously during ICIs treatment and up to 30 days after the last dose by using the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Complications related to ablation procedure were assessed peri-operation period and reported according to the standardized Society of Interventional Radiology grading system.
  • 2. Response [ Time Frame: 6-8 weeks ]
    Efficacy included objective response (includes complete and partial response), duration of response, and disease control (Includes complete and partial response, stable disease and atypical progression for at least 3 months).
  • Secondary Outcome Measures: 1. Time to tumor progression [ Time Frame: 3-4 months ]
    time from first dose of ICIs drug until the first typical progression of disease
  • 2. Progression-free survival [ Time Frame: 3-4 months ]
    time from first day of ICIs treatment to first typical disease progression, or death, which occurred earlier
  • 3. Overall survival [ Time Frame: 3-4 months ]
    time from first study treatment to death of any cause

Eligibility Criteria

  • Ages Eligible for Study: 18 to 80 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Locations

China, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou

Sponsors and Collaborators

Sun Yat-sen University

Investigators

Principal Investigator: Ming Zhao, MD, Ph.D Sun Yat-sen University

More Information

  • Responsible Party: Sun Yat-sen University
  • ClinicalTrials.gov Identifier: NCT03939975 History of Changes
  • Other Study ID Numbers: B2018-151-01
  • First Posted: May 7, 2019 Key Record Dates
  • Last Update Posted: August 19, 2019
  • Last Verified: August 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Keywords provided by Sun Yat-sen University: Microwave ablation
    Hepatocellular carcinoma
    Immunotherapy
    Nivolumab
    Pembrolizumab
    Radiofrequency Ablation
  • Additional relevant MeSH terms: Carcinoma Carcinoma, Hepatocellular