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Infusion of PD1/PDL1 Inhibitor Via Hepatic Arterial Versus Vein for Immunotherapy of Advanced Hepatocellular Carcinoma

Primary Purpose

Liver Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
PD1/PDL1 inhibitor
Sponsored by
Second Affiliated Hospital of Guangzhou Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring Liver Cancer, PD1 antibody, Artery infusion, PDL1 antibody

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Cytohistological confirmation is required for diagnosis of HCC.、
  2. Signed informed consent before recruiting
  3. Age between 18 to 80 years with estimated survival over 3 months.
  4. Child-Pugh class A or B/Child score > 7; ECOG score < 2
  5. Tolerable coagulation function or reversible coagulation disorders
  6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L
  7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
  8. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
  9. Birth control.
  10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

  1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
  2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
  3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
  4. Patients accompanied with other tumors or past medical history of malignancy;
  5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;

  6. Patients have poor compliance.

    Any contraindications for hepatic arterial infusion procedure:

    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).

  7. Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;
  8. Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol;
  9. Any agents which could affect the absorption or pharmacokinetics of the study drugs
  10. Subjects unable to suffer the discomfort of the HAI procedure

Sites / Locations

  • The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

PD1/PDL1 inhibitor hepatic artery infusion

PD1/PDL1 inhibitor vein infusion

Arm Description

Interventional technique to place microcatheter in hepatic artery to infuse PD1/PDL1 inhibitor in 30 minutes.

Regular IV infusion of PD1/PDL1 inhibitor in 30 minutes.

Outcomes

Primary Outcome Measures

Overall survival
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.

Secondary Outcome Measures

Progression-free survival
Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.
Adverse event rate
Adverse event rate will be defined as the rate of patients who developed adverse event.

Full Information

First Posted
May 13, 2019
Last Updated
February 26, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03949231
Brief Title
Infusion of PD1/PDL1 Inhibitor Via Hepatic Arterial Versus Vein for Immunotherapy of Advanced Hepatocellular Carcinoma
Official Title
A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1 Inhibitor Via Hepatic Arterial Infusion Versus Vein for Immunotherapy of Advanced Liver Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 2, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial was designed to investigate the survival outcomes, response rates, and safety of patients with Barcelona-Clinical Hepatocellular Carcinoma (BCLC)-C-stage liver cancer by hepatic artery versus vein infusion of PD1/PDL1 inhibitor.
Detailed Description
Liver cancer is the fifth most common malignancy worldwide, but the mortality rate ranks third. China has a large population base, with more than 400,000 new cases each year, and more than half of the world's new liver cancer and deaths. More than 70% of liver cancer patients in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Only 10%-15% of newly diagnosed patients can undergo radical resection, and the recurrence rate after 5 years is as high as 50%-80%. So far, sorafenib is still the only standard treatment that can prolong the overall survival of advanced hepatocellular carcinoma. SHARP's latest research shows that sorafenib can only extend patients with advanced liver cancer for 2.8 months, and many adverse reactions; regofenib can be used in patients with advanced liver cancer after taking sorafenib resistance, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced liver cancer, and more alternative therapies are urgently needed. PD1/PDL1 inhibitor is widely used in treatment of various cancers in China now. The hepatic arterial chemotherapy infusion for advanced liver cancer, through the "first pass effect" of drug treatment, can significantly increase the local drug concentration of the tumor, improve the efficacy, reduce systemic adverse reactions, meanwhile Folfox regimen has been confirmed by the hepatic arterial chemotherapy infusion program. To the investigator's knowledge, no studies have been developed on the survival benefit of hepatic arterial infusion of immunotherapeutic agents in patients with advanced liver cancer. This phase III clinical trial was designed to compare the effects of PD1/PDL1 inhibitor via IA and IV on the survival benefit of patients with advanced liver cancer, including ORR, DCR, median survival time, and safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer
Keywords
Liver Cancer, PD1 antibody, Artery infusion, PDL1 antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PD1/PDL1 inhibitor hepatic artery infusion
Arm Type
Experimental
Arm Description
Interventional technique to place microcatheter in hepatic artery to infuse PD1/PDL1 inhibitor in 30 minutes.
Arm Title
PD1/PDL1 inhibitor vein infusion
Arm Type
Experimental
Arm Description
Regular IV infusion of PD1/PDL1 inhibitor in 30 minutes.
Intervention Type
Drug
Intervention Name(s)
PD1/PDL1 inhibitor
Other Intervention Name(s)
Administration of PD1/PDL1 inhibitor through vein or interventional technique.
Intervention Description
Infusion of PD1/PDL1 inhibitor through peripheral vein or hepatic artery.
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.
Time Frame
2 years
Title
Adverse event rate
Description
Adverse event rate will be defined as the rate of patients who developed adverse event.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytohistological confirmation is required for diagnosis of HCC.、 Signed informed consent before recruiting Age between 18 to 80 years with estimated survival over 3 months. Child-Pugh class A or B/Child score > 7; ECOG score < 2 Tolerable coagulation function or reversible coagulation disorders Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy. Birth control. Willing and able to comply with scheduled visits, treatment plan and laboratory tests. 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. Any contraindications for hepatic arterial infusion procedure: 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). Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on; Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol; Any agents which could affect the absorption or pharmacokinetics of the study drugs Subjects unable to suffer the discomfort of the HAI procedure
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Lian, MD
Phone
02034153532
Email
lian-hui-2008@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhenfeng Zhang, MD, PhD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hui Lian, MD
Organizational Affiliation
Second Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PhD
Organizational Affiliation
Second Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Guangzhou Medical University
City
Guanzhou
State/Province
Guangdong
ZIP/Postal Code
51260
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui Lian, MD
Phone
02034153532
Email
lian-hui-2008@163.com
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PhD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Hui Lian, MD
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PHD

12. IPD Sharing Statement

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Infusion of PD1/PDL1 Inhibitor Via Hepatic Arterial Versus Vein for Immunotherapy of Advanced Hepatocellular Carcinoma

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