Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: IT injection of double ICIs | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs only. |
|
| Group 2: IT injection of double ICIs and chemodrug | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug. |
|
| Group 3: IT injection of double ICIs and chemodrug plus bevacizumab | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| pCR 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. | 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. | Six months |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity of the study groups | Toxicity is assessed by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4. | Six months |
| Response rates to neoadjuvant treatment |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
Patients accompanied with other tumors or past medical history of malignancy;
Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
Patients have poor compliance. A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (> 160/100 mm/Hg).
Allergic to contrast agent;
Any agents which could affect the absorption or pharmacokinetics of the study drugs
Other conditions that investigator decides not suitable for the trial.
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhenfeng Zhang, MD, PhD | Contact | +862039195966 | zhangzhf@gzhmu.edu.cn | |
| Bingjia He, MD | Contact | +862039195965 | 464677938@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Zhenfeng Zhang, MD, PhD | Second Affiliated Hospital of Guangzhou Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Affiliated Hospital of Guangzhou Medical University | Recruiting | Guanzhou | Guangdong | 51260 | China |
Not provided
| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000074324 | Ipilimumab |
| C582435 | pembrolizumab |
| C000613593 | durvalumab |
| D015255 | Idarubicin |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
Response rates are assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1.
| Six years |
| Recurrence-free survival | Recurrence-free survival is measured as routine. | Six years |
| Overall survival | To correlate major pathologic response with recurrence-free and overall survival. | Six years |
| D008107 |
| Liver Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |