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

NCT04233840 | Unknown Phase 1 DMC

• 1 other identifier: 201710061MIPB
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Keywords

P1101; Anti-PD1; HCC; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• 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

Study Arms (4)

Sequential administration of P1101 and anti-PD1

EXPERIMENTAL

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); Drug: Nivolumab

anti-PD1

ACTIVE COMPARATOR

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

Drug: Nivolumab

P1101 monotherapy

ACTIVE COMPARATOR

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

Drug: P1101 (Ropeginterferon alfa-2b)

sequential administration of P1101 and anti-PD1

EXPERIMENTAL

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); Drug: Nivolumab

Interventions

P1101 (Ropeginterferon alfa-2b) DRUG

solution for injection in prefilled syringe, 500 µg/ mL , 450μg /time, subcutaneous injection every 2 weeks

P1101 monotherapy; Sequential administration of P1101 and anti-PD1; sequential administration of P1101 and anti-PD1

Nivolumab DRUG

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

Also known as: Opdivo

Sequential administration of P1101 and anti-PD1; anti-PD1; sequential administration of P1101 and anti-PD1

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ;

You may not qualify if:

• 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;

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• PharmaEssentia: collaborator

Study Sites (1)

National Taiwan university Hospital

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pei-Jer Chen

  NTUH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pei-Jer Chen

CONTACT

886-2-23123456; peijerchen@ntu.edu.tw

Shu-Fen Chang

CONTACT

886-2-23819903; booksun1013@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I : Dose escalation study with Anti-PD1 dossages 4 cohorts Phase II : 3 parallel arms

Study Record Dates

• First Submitted: December 26, 2019
• First Posted: January 18, 2020
• Study Start: February 12, 2019
• Primary Completion: December 31, 2022
• Study Completion: July 31, 2023
• Last Updated: January 27, 2022

Record last verified: 2021-02

Locations

TW (1)