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

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
P1101 (Ropeginterferon alfa-2b)
Nivolumab
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring P1101, Anti-PD1, HCC, Hepatocellular Carcinoma

Eligibility Criteria

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

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;

Sites / Locations

  • National Taiwan university HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Experimental

Arm Label

Sequential administration of P1101 and anti-PD1

anti-PD1

P1101 monotherapy

sequential administration of P1101 and anti-PD1

Arm Description

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

Phase II Study Group I: anti-PD1 arm 3mg/kg 3 doses

Phase II Study Group II: P1101 arm 450mcg 12 doses

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)

Outcomes

Primary Outcome Measures

Phase I portion - Dose-limiting Toxicity
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).
Phase II portion - Recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first)
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

Secondary Outcome Measures

Disease-free survival
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
Recurrence-free survival
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
HBsAg level
To assess the change in mean HBsAg level from baseline at the end of treatment (EOT), 24 weeks and 48 weeks after randomization

Full Information

First Posted
December 26, 2019
Last Updated
January 25, 2022
Sponsor
National Taiwan University Hospital
Collaborators
PharmaEssentia
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1. Study Identification

Unique Protocol Identification Number
NCT04233840
Brief Title
P1101 and Anti-PD1 for After Curative Surgery of Hepatitis B-related Hepatocellular Carcinoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 12, 2019 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
Collaborators
PharmaEssentia

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
P1101, Anti-PD1, HCC, Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase I : Dose escalation study with Anti-PD1 dossages 4 cohorts Phase II : 3 parallel arms
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sequential administration of P1101 and anti-PD1
Arm Type
Experimental
Arm Description
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
Arm Title
anti-PD1
Arm Type
Active Comparator
Arm Description
Phase II Study Group I: anti-PD1 arm 3mg/kg 3 doses
Arm Title
P1101 monotherapy
Arm Type
Active Comparator
Arm Description
Phase II Study Group II: P1101 arm 450mcg 12 doses
Arm Title
sequential administration of P1101 and anti-PD1
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
P1101 (Ropeginterferon alfa-2b)
Intervention Description
solution for injection in prefilled syringe, 500 µg/ mL , 450μg /time, subcutaneous injection every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
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
Primary Outcome Measure Information:
Title
Phase I portion - Dose-limiting Toxicity
Description
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).
Time Frame
18 weeks
Title
Phase II portion - Recurrence-free survival (defined as the time from randomization to HCC recurrence or death from any cause, whichever occured first)
Description
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
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
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
Time Frame
48 weeks
Title
Recurrence-free survival
Description
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
Time Frame
96 weeks
Title
HBsAg level
Description
To assess the change in mean HBsAg level from baseline at the end of treatment (EOT), 24 weeks and 48 weeks after randomization
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject with HCC who meet the following criteria 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; Subjects with the primary occurrence HCC ; 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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pei-Jer Chen
Phone
886-2-23123456
Ext
67072
Email
peijerchen@ntu.edu.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Shu-Fen Chang
Phone
886-2-23819903
Email
booksun1013@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pei-Jer Chen
Organizational Affiliation
NTUH
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Taiwan university Hospital
City
Taipei city
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pei-Jer Chen
Phone
886-2-23123456
Ext
67072
Email
peijerchen@ntu.edu.tw
First Name & Middle Initial & Last Name & Degree
Shu-Fen Chang
Phone
886-2-23819903
Email
booksun1013@gmail.com

12. IPD Sharing Statement

Learn more about this trial

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

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