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Pembrolizumab as Neoadjuvant Treatment in HCC

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Sponsored by
Kindai University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma, Neo adjuvant chemotherapy, Adjuvant chemotherapy, Immune checkpoint inhibitor, Pembrolizumab

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Hepatocellular carcinoma for which radical cure is possible by resection or RFA.
  • Diagnosed with typical HCC based on imaging findings with Intermediate or High Risk of recurrence as assessed by tumor characteristics.
  • Male or female subjects >/= 20 years of age
  • Child-Pugh score A
  • ECOG Performance Status of 0.
  • Adequate bone marrow, liver and renal function

Exclusion Criteria:

  • Recurrent HCC
  • HCC with extrahepatic metastasis and/or vascular invasion confirmed by diagnostic imaging
  • Subjects with poorly controlled ascites (excluding cases that responded to diuretic therapy)
  • Subjects with hepatic encephalopathy
  • Past history of immunotherapy
  • Past history or complication of an active autoimmune disorder.
  • Past history or complication of interstitial pneumonia.
  • Past or current history of malignant tumor, except for curative cases
  • Subjects with renal insufficiency requiring hemodialysis or peritoneal dialysis.
  • Past or current history of severe cardiovascular disease
  • Active clinically serious infections except for HBV or HCV
  • Subjects with convulsive disorder requiring treatment (risk of convulsive seizures).
  • Subjects with gastrointestinal bleeding causing clinical problems within a 4-week period before enrollment in this study.
  • Subjects with thrombosis or embolism that developed within a 6-month period before enrollment in this study
  • Subjects with pregnant or breast feeding, or planning to become a parent
  • Subjects with possible allergic reaction to the investigational drug.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Pembrolizumab

    Arm Description

    Pembrolizumab 200 mg IV once only in the neoadjuvant phase. Pembrolizumab 200 mg IV every 3 weeks in the adjuvant phase.

    Outcomes

    Primary Outcome Measures

    One-year recurrence-free survival rate
    One-year recurrence-free survival rate is defined as the recurrence-free survival rate 1year after curative treatment.

    Secondary Outcome Measures

    Recurrence free survival
    Recurrence-free survival is defined as the length of time from the date of confirmation of complete cure to the earliest of the following: the date when recurrence is diagnosed or the date of death due to any cause.
    Overall survival
    Overall survival is defined as the length of time from the date of confirmation of complete cure to the date of death due to any cause.
    Objective response rate after neoadjuvant phase
    Tumor assessment in accordance with RECIST1.1 will be performed after neoadjuvant administration.
    Tumor markers
    Baseline levels of tumor markers including AFP, AFP-L3, and PIVKA-II and changes in their levels will be exploratory investigated in relation to the therapy efficacy.
    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
    The safety endpoints of this study are the safety of pembrolizumab as neoadjuvant and/or adjuvant therapy in patients with HCC. To determine the safety of the drug, the degree of toxicity is evaluated in accordance with the CTCAE (version 4.0).

    Full Information

    First Posted
    October 30, 2017
    Last Updated
    November 8, 2017
    Sponsor
    Kindai University
    Collaborators
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03337841
    Brief Title
    Pembrolizumab as Neoadjuvant Treatment in HCC
    Official Title
    Neoadjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma With Pembrolizumab Trial (AURORA)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2017
    Overall Recruitment Status
    Unknown status
    Study Start Date
    November 10, 2017 (Anticipated)
    Primary Completion Date
    October 31, 2019 (Anticipated)
    Study Completion Date
    October 31, 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Kindai University
    Collaborators
    Merck Sharp & Dohme LLC

    4. Oversight

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

    5. Study Description

    Brief Summary
    The aim of this study is to elucidate the utility of the immune checkpoint inhibitor pembrolizumab in preventing the recurrence of HCC when administered before and after curative surgery or ablation.
    Detailed Description
    Each subject will participate in the trial from the time he or she signs the informed consent form until the final contact. After a screening phase of up to 28 days, each subject will receive administration of pembrolizumab 200mg IV once only before curative treatment such as hepatic resection or radiofrequency ablation, and will receive curative treatment after administration of pembrolizumab. After curative treatment, each subject will receive pembrolizumab 200mg IV every 3 weeks. Treatment will continue until tumor recurrence, occurrence of an unacceptable adverse event, or the 16th treatment with pembrolizumab.( The setting of 16 times administration is the period of adjuvant therapy of this trial is 12 month(=48weeks), administration of pembrolizumab is Q3W, so 16 times administration comes to 48 weeks.) Subjects who discontinue for reasons other than tumor recurrence will have post-treatment follow-up visits for monitoring disease status until tumor recurrence, until initiation of non-study cancer treatment, until withdrawal of consent for study participation, or until becoming lost to follow-up. All subjects will be followed for overall survival until death, withdrawal of consent for study participation, or the end of the study, whichever comes first. After the end of trial treatment, each subject will be followed for 30 days for adverse event monitoring. Serious adverse events will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatocellular Carcinoma
    Keywords
    Hepatocellular carcinoma, Neo adjuvant chemotherapy, Adjuvant chemotherapy, Immune checkpoint inhibitor, Pembrolizumab

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Pembrolizumab
    Arm Type
    Experimental
    Arm Description
    Pembrolizumab 200 mg IV once only in the neoadjuvant phase. Pembrolizumab 200 mg IV every 3 weeks in the adjuvant phase.
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    MK-3475, Keytruda
    Intervention Description
    Each subject will receive administration of pembrolizumab 200mg IV once only before curative treatment such as hepatic resection or radiofrequency ablation, and will receive curative treatment after administration of pembrolizumab. After curative treatment, each subject will receive pembrolizumab 200mg IV every 3 weeks. Treatment will continue until tumor recurrence, occurrence of an unacceptable adverse event, or the 16th treatment with pembrolizumab.( The setting of 16 times administration is the period of adjuvant therapy of this trial is 12 month(=48weeks), administration of pembrolizumab is Q3W, so 16 times administration comes to 48 weeks.)
    Primary Outcome Measure Information:
    Title
    One-year recurrence-free survival rate
    Description
    One-year recurrence-free survival rate is defined as the recurrence-free survival rate 1year after curative treatment.
    Time Frame
    1 year after curative treatment
    Secondary Outcome Measure Information:
    Title
    Recurrence free survival
    Description
    Recurrence-free survival is defined as the length of time from the date of confirmation of complete cure to the earliest of the following: the date when recurrence is diagnosed or the date of death due to any cause.
    Time Frame
    From the date of enrollment until the date of first recurrence or date of death from any cause, whichever came first, up to 72 weeks.
    Title
    Overall survival
    Description
    Overall survival is defined as the length of time from the date of confirmation of complete cure to the date of death due to any cause.
    Time Frame
    From date of enrollment until the date of death from any cause, up to 72 weeks.
    Title
    Objective response rate after neoadjuvant phase
    Description
    Tumor assessment in accordance with RECIST1.1 will be performed after neoadjuvant administration.
    Time Frame
    Evaluation period is just before curative treatment, up to 4 weeks.
    Title
    Tumor markers
    Description
    Baseline levels of tumor markers including AFP, AFP-L3, and PIVKA-II and changes in their levels will be exploratory investigated in relation to the therapy efficacy.
    Time Frame
    From the date of enrollment until the date of last administration of study drug, up to 72 weeks.
    Title
    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
    Description
    The safety endpoints of this study are the safety of pembrolizumab as neoadjuvant and/or adjuvant therapy in patients with HCC. To determine the safety of the drug, the degree of toxicity is evaluated in accordance with the CTCAE (version 4.0).
    Time Frame
    From the date of enrollment until the date of last administration of study drug, thereafter up to 4 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Hepatocellular carcinoma for which radical cure is possible by resection or RFA. Diagnosed with typical HCC based on imaging findings with Intermediate or High Risk of recurrence as assessed by tumor characteristics. Male or female subjects >/= 20 years of age Child-Pugh score A ECOG Performance Status of 0. Adequate bone marrow, liver and renal function Exclusion Criteria: Recurrent HCC HCC with extrahepatic metastasis and/or vascular invasion confirmed by diagnostic imaging Subjects with poorly controlled ascites (excluding cases that responded to diuretic therapy) Subjects with hepatic encephalopathy Past history of immunotherapy Past history or complication of an active autoimmune disorder. Past history or complication of interstitial pneumonia. Past or current history of malignant tumor, except for curative cases Subjects with renal insufficiency requiring hemodialysis or peritoneal dialysis. Past or current history of severe cardiovascular disease Active clinically serious infections except for HBV or HCV Subjects with convulsive disorder requiring treatment (risk of convulsive seizures). Subjects with gastrointestinal bleeding causing clinical problems within a 4-week period before enrollment in this study. Subjects with thrombosis or embolism that developed within a 6-month period before enrollment in this study Subjects with pregnant or breast feeding, or planning to become a parent Subjects with possible allergic reaction to the investigational drug.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kazuomi Ueshima, Lecturer
    Phone
    +81-72-366-0221
    Ext
    3525
    Email
    kaz-ues@med.kindai.ac.jp
    First Name & Middle Initial & Last Name or Official Title & Degree
    Masatoshi Kudo, Professor
    Phone
    +81-72-366-0221
    Ext
    3149
    Email
    m-kudo@med.kindai.ac.jp
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Masatoshi Kudo, Professor
    Organizational Affiliation
    Kindai University Faculty of Medicine, Gastroenterology and Hepatology
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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