P1101 and Anti-PD1 for After Curative Surgery of Hepatitis B-related Hepatocellular Carcinoma

January 25, 2022 updated by: National Taiwan University Hospital

A Phase I/II Open Label Study to Evaluate Safety and the Prophylactic Effect on Recurrence of Anti-PD1 Monotherapy, P1101 Monotherapy, and Sequential Administration of P1101 and Anti-PD1 After Curative Surgery of HBV-related HCC

The main purpose of this trial is to evaluate the safety of the new adjuvant treatment of curative HCC, or the treatment of long-acting interferon P1101 alone, or the use of long-acting interferon P1101 and subsequent treatment of anti-PD1, and any efficacy in reducing the recurrence rate of patients after surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

secondary end-point: P1101 and anti-PD1 sequential therapy on hepatitis B (especially on HbsAg).

Study Type

Interventional

Enrollment (Anticipated)

72

Phase

  • Phase 2
  • Phase 1

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

Study Locations

  • Taiwan
      • Taipei city, Taiwan, 100
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
        • Contact:

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:

  • Subject with HCC who meet the following criteria

    1. Subjects diagnosed as having typical HCC on dynamic CT, or dynamic MRI performed within 8 weeks before surgery, or subjects who diagnosed HCC by pathology after surgery resection;
    2. Subjects with the primary occurrence HCC ;
    3. Subjects with the HCC related to hepatitis B virus (HBV) ;
  • Subject who have undergone surgical liver reaction within 8 weeks prior to study entry.
  • Subjects showing a complete cure shows no findings suggestive of recurrence or remnant. ;
  • Subject who are able to begin treatment with the study drug within 12 weeks after liver surgery resection. ;
  • Subjects confirmed of satisfying the following conditions based on the screening performed at enrollment: Positive for HBsAg/ Undetectable HBV DNA, with or without current anti HBV treatment/ Grade A on Child-Pugh classification;
  • Normal fundoscopic examination by ophthalmologist at screening;
  • ECOG 0 to 1 ;

Exclusion Criteria:

  • Subjects positive for anti-HCV ;
  • Subjects showing vascular invasion of HCC on imaging diagnosis ;
  • Subjects who have uncontrolled hypertension;
  • Subjects with a history of pneumonitis or interstitial lung disease . cardiac arrest . an active infection requiring therapy .;
  • Diabetes mellitus with HbA1c ≥ 7.4% with insulin treatment;

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sequential administration of P1101 and anti-PD1

Phase I of Study : To determine the safety, tolerability, DLT, and potential phase 2 dose of sequential administration of P1101 and anti-PD1

:Sequential administration 6 doses (450mcg) of P1101 and 3 doses of anti-PD1 (Escalating from 0.3, 0.75, 1.5, 3 mg/kg) for Phase I Study
Drug: P1101 (Ropeginterferon alfa-2b)
solution for injection in prefilled syringe, 500 µg/ mL , 450μg /time, subcutaneous injection every 2 weeks
Drug: Nivolumab

Phase I study will use 0.3, 0.75, 1.5, 3mg/kg, Q2W for 3 doses after 6 doses of P1101.

Phase II study : Group I will use 3mg/kg, Q2W for 3 doses; Group III will use the dosage that determine from Phase I study 3 doses after 6 doses of P1101

Other Names:
  • Opdivo
Active Comparator: anti-PD1
Phase II Study Group I: anti-PD1 arm 3mg/kg 3 doses
Drug: Nivolumab

Phase I study will use 0.3, 0.75, 1.5, 3mg/kg, Q2W for 3 doses after 6 doses of P1101.

Phase II study : Group I will use 3mg/kg, Q2W for 3 doses; Group III will use the dosage that determine from Phase I study 3 doses after 6 doses of P1101

Other Names:
  • Opdivo
Active Comparator: P1101 monotherapy
Phase II Study Group II: P1101 arm 450mcg 12 doses
Drug: P1101 (Ropeginterferon alfa-2b)
solution for injection in prefilled syringe, 500 µg/ mL , 450μg /time, subcutaneous injection every 2 weeks
Experimental: sequential administration of P1101 and anti-PD1
Phase II Study GroupIII:Sequential administration of 6 doses of 450mcg P1101 and followed by 3 doses of anti-PD1 dosage (base on Phase I study result)
Drug: P1101 (Ropeginterferon alfa-2b)
solution for injection in prefilled syringe, 500 µg/ mL , 450μg /time, subcutaneous injection every 2 weeks
Drug: Nivolumab

Phase I study will use 0.3, 0.75, 1.5, 3mg/kg, Q2W for 3 doses after 6 doses of P1101.

Phase II study : Group I will use 3mg/kg, Q2W for 3 doses; Group III will use the dosage that determine from Phase I study 3 doses after 6 doses of P1101

Other Names:
  • Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I portion - Dose-limiting Toxicity
Time Frame: 18 weeks
To determine the potential phase 2 dose of sequestial administration of P1101 and anti-PD1. The MTD is determine by the prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).
18 weeks
Phase II portion - Recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first)
Time Frame: 48 weeks
To evaluate safety(assessment of AE, SAE and unanticipated problem) and the recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first) at 48 weeks after randomization of anti-PD 1 monotherapy, P1101 monotherapy, and sequential administration of P1101 and anti-PD 1 therapy arms
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: 48 weeks
To assess the effect of anti-PD1 monotherapy, P1101 monotherapy, and sequential administration of P1101 and anti-PD1 in inhibiting the recurrence, using disease-free survival (defined as the time from randomization to HCC recurrence, death from any cause, or onset of secondary tumor, whichever occurred first) at 48 weeks after randomization as the endpoint
48 weeks
Recurrence-free survival
Time Frame: 96 weeks
To assess the treatment effect of anti-PD1 monotherapy, P1101 monotherapy, or sequential administration of P1101 and anti-PD1 in inhibiting the recurrence, using recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occurred first) at 96 weeks after randomization as the endpoint
96 weeks
HBsAg level
Time Frame: End of treatment of Anti-PD1 arm is up to 6 weeks; End of treatment of P1101 arm is up to 24 weeks; End of treatment of sequential administration of P1101 and anti-PD1 is up to 18 weeks, 24 weeks and 48 weeks
To assess the change in mean HBsAg level from baseline at the end of treatment (EOT), 24 weeks and 48 weeks after randomization
End of treatment of Anti-PD1 arm is up to 6 weeks; End of treatment of P1101 arm is up to 24 weeks; End of treatment of sequential administration of P1101 and anti-PD1 is up to 18 weeks, 24 weeks and 48 weeks

Collaborators and Investigators

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

Sponsor

National Taiwan University Hospital

Collaborators

PharmaEssentia

Investigators

  • Principal Investigator: Pei-Jer Chen, NTUH

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 (Actual)

February 12, 2019

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

July 31, 2023

Study Registration Dates

First Submitted

December 26, 2019

First Submitted That Met QC Criteria

January 15, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Actual)

January 27, 2022

Last Update Submitted That Met QC Criteria

January 25, 2022

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201710061MIPB

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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