Pembrolizumab as Neoadjuvant Treatment in HCC

November 8, 2017 updated by: Masatoshi Kudo, Kindai University

Neoadjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma With Pembrolizumab Trial (AURORA)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab
Pembrolizumab 200 mg IV once only in the neoadjuvant phase. Pembrolizumab 200 mg IV every 3 weeks in the adjuvant phase.
Drug: Pembrolizumab
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.)
Other Names:
  • Keytruda
  • MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
One-year recurrence-free survival rate
Time Frame: 1 year after curative treatment
One-year recurrence-free survival rate is defined as the recurrence-free survival rate 1year after curative treatment.
1 year after curative treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence free survival
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.
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.
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.
Overall survival
Time Frame: From date of enrollment until the date of death from any cause, up to 72 weeks.
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.
From date of enrollment until the date of death from any cause, up to 72 weeks.
Objective response rate after neoadjuvant phase
Time Frame: Evaluation period is just before curative treatment, up to 4 weeks.
Tumor assessment in accordance with RECIST1.1 will be performed after neoadjuvant administration.
Evaluation period is just before curative treatment, up to 4 weeks.
Tumor markers
Time Frame: From the date of enrollment until the date of last administration of study drug, up to 72 weeks.
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.
From the date of enrollment until the date of last administration of study drug, up to 72 weeks.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: From the date of enrollment until the date of last administration of study drug, thereafter up to 4 months
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).
From the date of enrollment until the date of last administration of study drug, thereafter up to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kindai University

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Masatoshi Kudo, Professor, Kindai University Faculty of Medicine, Gastroenterology and Hepatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 10, 2017

Primary Completion (Anticipated)

October 31, 2019

Study Completion (Anticipated)

October 31, 2020

Study Registration Dates

First Submitted

October 30, 2017

First Submitted That Met QC Criteria

November 8, 2017

First Posted (Actual)

November 9, 2017

Study Record Updates

Last Update Posted (Actual)

November 9, 2017

Last Update Submitted That Met QC Criteria

November 8, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AURORA study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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