The purpose of this study is to determine the safety and efficacy of immunotherapy toripalimab (anti-PD-1 mAb) combined with thermal ablation in patients with Hepatocellular Carcinoma (HCC).
1.1 Primary Objective \& Hypothesis Determine the safety and efficacy of radiofrequency ablation (RFA)/microwave ablation (MWA) followed by toripalimab for advanced HCC by establishing the rates of toxicity that occur within 6 months after ablation. Hypothesis: Thermal ablation followed by toripalimab will have similar toxicity to toripalimab monotherapy. Thermal ablation enhances antitumor immune response and improves the best overall response rate compared to historical controls with toripalimab alone. 1.2 Secondary Objectives and Hypotheses Estimate the progression-free survival, and overall survival. Hypothesis: Disease control and survival will be better than that observed with toripalimab monotherapy. 1.3 Exploratory Objectives Explore changes in inflammatory biomarkers (including, but not limited to CD8+/Treg ratio, total CD4+ counts, total lymphocyte count) in pretreatment and on-treatment serially collected peripheral blood samples. Hypothesis: Changes in inflammatory biomarkers after thermal ablation may correlate with a more favorable response to immunotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
145
Radiofrequency ablation or microwave ablation is performed under CT or ultrasound guidance for one to five target lesions.
Protocol 1. Patients received toripalimab (240mg, Q3W) as monotherapy. Protocol 2. Patients received toripalimab (240mg, Q3W) on day 3 after ablation. Protocol 3. Patients received toripalimab (240mg, Q3W) on day 14 after ablation.
Xiangya Hospital, Central South University
Changsha, Hunan, China
Progression free survival
From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first.
Time frame: Up to approximately 3 years
Overall response rate
Treatment evaluation will be done using mRECIST
Time frame: Up to approximately 2 years
Overall survival
From random date to death for any reason.
Time frame: Up to approximately 3 years
Disease Control Rate
Defined as the percentage of patients who have achieved complete response, partial response and stable disease
Time frame: Up to approximately 3 years
Number of participants with adverse events
Evaluation will be done using NCI-CTCAE (version 4.03).
Time frame: Up to approximately 3 years
Tumour marker response
Percentage of AFP variation
Time frame: Up to approximately 3 years
The time to deterioration of quality of life
Repetitive decreases of 10 points or more from the baseline of the EORTC QLQ-C30 for two consecutive assessments or a decrease of 10 points or more in a single assessment followed by death from any cause within three weeks.
Time frame: Up to approximately 3 years
Duration of response
the time from first documented complete or partial response to disease progression or death) according to investigator-assessed and independently-assessed mRECIST criteria
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Time frame: Up to approximately 2 years
The general health status
The Eastern Cooperative Oncology Group (ECOG) was applied to assess the general health status of the patients.
Time frame: Up to approximately3 years