This trial is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection.
Antibodies against CTLA4, PD1 or PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for hepatocellular carcinoma (HCC) via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as neoaduvant therapy on patients with HCC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
This study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times.
The Second Affiliated Hospital of Guangzhou Medical University
Guanzhou, Guangdong, China
RECRUITINGpCR rate for the study groups
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
Time frame: Six months
mPR rate for the study groups
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
Time frame: Six months
Toxicity of the study groups
Toxicity is assessed by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.
Time frame: Six months
Response rates to neoadjuvant treatment
Response rates are assessed by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1.
Time frame: Six years
Recurrence-free survival
Recurrence-free survival is measured as routine.
Time frame: Six years
Overall survival
To correlate major pathologic response with recurrence-free and overall survival.
Time frame: Six years
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