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Infusion of Keytruda Via Hepatic Arterial Versus Vein for Immunotherapy of Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT03755739
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

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 infusion of Pembrolizumab and Nivolumab and to compare their differences.

Condition or disease Intervention/treatment Phase
Hepatocarcinoma Drug: Pembrolizumab Not Applicable

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.

Pembrolizumab and Nivolumab are representative drugs for immunosuppressive agents, and their indications have been approved in various types of tumors, including advanced melanoma, advanced squamous non-small cell lung cancer, advanced renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients.In September 2017, Nivolumab was approved for second-line treatment after sorafenib resistance. Part of the results of the CheckMate040 study showed that the median survival of the graded dose group was 15.0 months. 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 immunosuppressive agents in patients with advanced liver cancer, and there is no comparative study of randomized controls of two immunosuppressive agents. This phase III clinical trial was designed to compare the effects of Pembrolizumab and Nivolumab on the survival benefit of patients with advanced liver cancer, including ORR, DCR, median survival time, and safety.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Comparison of Survival Benefit of Administration of Keytruda Via Hepatic Arterial Infusion Versus Vein for Immunotherapy of Advanced Liver Cancer
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab TAI

This group dividied into two subgroups:

  1. Pembrolizumab is administrated with a total dose of 2mg/kg via sustained (30min) micro-pump implantation, every 3 weeks.
  2. Pembrolizumab is administrated with a total dose of 2mg/kg via sustained (24h) micro-pump implantation, every 3 weeks.
Drug: Pembrolizumab
Hepatic artery infusion of immunotherapy agent
Other Name: Keytruda

Pembrolizumab vein infusion
Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30min), every 3 weeks.
Drug: Pembrolizumab
Hepatic artery infusion of immunotherapy agent
Other Name: Keytruda




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
    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 :
  1. Progression-free survival [ Time Frame: 2 years ]
    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.

  2. Adverse event rate [ Time Frame: 2 years ]
    Adverse event rate will be defined as the rate of patients who developed adverse event.

  3. Time to Intrahepatic tumor Progression [ Time Frame: 2 years ]
    Time to Intrahepatic tumor Progression was defined as the time from commencement of treatment to radiological intrahepatic tumor progression.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Cytohistological confirmation is required for diagnosis of HCC.、
  2. Signed informed consent before recruiting
  3. Age between 18 to 75 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03755739


Contacts
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Contact: Zhenfeng Zhang, MD,PhD 02034153532 zhangzhf@gzhmu.edu.cn
Contact: Deji Chen, MD,PhD 02034153532 chendeji2003@163.com

Locations
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China, Guangdong
The Second Affiliated Hospital of Guangzhou Medical University Recruiting
Guanzhou, Guangdong, China, 51260
Contact: Zhenfeng Zhang, MD,PhD    02034153532    zhangzhf@gzhmu.edu.cn   
Sponsors and Collaborators
Second Affiliated Hospital of Guangzhou Medical University
Investigators
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Principal Investigator: Zhenfeng Zhang, MD,PhD Second Affiliated Hospital of Guangzhou Medical University

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Responsible Party: Second Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT03755739     History of Changes
Other Study ID Numbers: Intra-artery Keytruda for HCC
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Second Affiliated Hospital of Guangzhou Medical University:
Hepatocarcinoma
Immunotherapy
HAI
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents