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
Overview
- Phase
- Phase 1
- Intervention
- P1101 (Ropeginterferon alfa-2b)
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- National Taiwan University Hospital
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Phase I portion - Dose-limiting Toxicity
- Last Updated
- 4 years ago
Overview
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).
Investigators
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;
Arms & Interventions
P1101 monotherapy
Phase II Study Group II: P1101 arm 450mcg 12 doses
Intervention: P1101 (Ropeginterferon alfa-2b)
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
Intervention: P1101 (Ropeginterferon alfa-2b)
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
Intervention: Nivolumab
anti-PD1
Phase II Study Group I: anti-PD1 arm 3mg/kg 3 doses
Intervention: Nivolumab
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)
Intervention: P1101 (Ropeginterferon alfa-2b)
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)
Intervention: Nivolumab
Outcomes
Primary Outcomes
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).
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
Secondary Outcomes
- Disease-free survival(48 weeks)
- Recurrence-free survival(96 weeks)
- HBsAg level(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)