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

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04233840
• Other study ID #: 201710061MIPB
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 12, 2019
• Est. completion date: July 31, 2023

Study information

• Verified date: February 2021
• Source: National Taiwan University Hospital
• Contact: Pei-Jer Chen
• Phone: 886-2-23123456
• Email: peijerchen[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: July 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• P1101 (Ropeginterferon alfa-2b)
solution for injection in prefilled syringe, 500 µg/ mL , 450µg /time, subcutaneous injection every 2 weeks
• 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

Locations

Country	Name	City	State
Taiwan	National Taiwan university Hospital	Taipei city

Sponsors (2)

Lead Sponsor	Collaborator
National Taiwan University Hospital	PharmaEssentia

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	18 weeks
Primary	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	48 weeks
Secondary	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	48 weeks
Secondary	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	96 weeks
Secondary	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	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