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Bevacizumab Biosimilar Plus FOLFOX4 in the Treatment of Recurrent HCC After Liver Transplantation

Primary Purpose

Post-orthotopic Liver Transplantation, Hepatocellular Carcinoma Recurrent

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Bevacizumab Biosimilar IBI305
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-orthotopic Liver Transplantation

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • adult patients with hepatocellular carcinoma who have received liver transplantation have postoperative radiographic or pathological evidence of recurrence;
  • have not received the first line of standard treatment or have received the first line of standard treatment failure;
  • at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 2;
  • Child-Pugh class A or B (Child-Pugh score ≤7 );
  • adequate organ function;
  • a predicted life expectancy of at least 3 months.

Exclusion Criteria:

  • allergy to the study drugs or their expedients or severe allergy to other monoclonal antibodies;
  • receipt of attenuated inactivated vaccines within 4 weeks of the start of the study or scheduled for such vaccination during the study;
  • evident concern of GI bleeding (local active ulcer, Guaic test at least ++) or a history of GI bleeding within the preceding 6 months;
  • uncontrolled pleural or peritoneal effusion;
  • pulmonary tuberculosis, sarcoidosis, HIV infection, or active HBV or HCV infection;
  • uncontrolled cardiac arrhythmia (including QTC interval ≥500 ms);
  • hepatic encephalopathy;
  • Known hepatocholangiocarcinoma, mixed hepatocellular and cholangiocellular carcinoma, fibrolamellar carcinoma, or a history of or concurrent cancer except cervical carcinoma in situ and cured basal cell carcinoma;
  • pregnant or lactating women or women contemplating pregnancy;
  • severe concomitant illness that jeopardizes patient safety or interferes with the completion of the study as deemed by the investigators;
  • esophageal or gastric variceal bleeding with portal hypertension within the past 6 months.

Sites / Locations

  • Jiangsu Province Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab combine with FOLFOX4

Arm Description

Bevacizumab biosimilar：7.5mg/kg，IV，D1，Q2W FOLFOX4： Oxaliplatin: 85 mg/m2 , IV, D1，Q2W Calcium leovorin: 200 mg/m2 ,IV, D1、D2，Q2W Fluorouracil: 400 mg/m2 push infusion and given 600mg/m2 intravenously 22 hours later， D1、D2, Q2W Treatment will continue until disease progression, an unacceptable toxicity, or the patient voluntarily discontinues the study, whichever comes first.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) ,Based on RECIST 1.1
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

Secondary Outcome Measures

Progression-free Survival (PFS), Based on RECIST 1.1 and mRECIST
PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on RECIST 1.1 and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
Disease Control Rate (DCR) ,Based on RECIST 1.1 and mRECIST
the proportion of patients who achieved CR, PR, or SD as their best overall response
Duration of Response (DOR) ,Based on RECIST 1.1 and mRECIST
From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years)
Overall Survival (OS)
From the date of first dose of study drug until date of death from any cause (up to approximately 2 years )
Time-to Response (TTR) Based on RECIST1.1 and mRECIST
TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST1.1 and mRECIST assessed by investigate.
Objective Response Rate (ORR) ,Based on mRECIST
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on mRECIST) assessed by investigator analysis.
Safety as measured by number and grade of adverse events
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Full Information

First Posted
April 20, 2022
Last Updated
May 5, 2022
Sponsor
The First Affiliated Hospital with Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05355155
Brief Title
Bevacizumab Biosimilar Plus FOLFOX4 in the Treatment of Recurrent HCC After Liver Transplantation
Official Title
An Exploratory Study of Bevacizumab Combined With FOLFOX4 in the Treatment of Recurrent Hepatocellular Carcinoma (HCC) After Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 1, 2022 (Anticipated)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a single arm, single center, prospective and open exploratory study. About 15 patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation are expected to be enrolled.Patients will be treated with bevacizumab and FOLFOX4.Treatment was continued until disease progression, development of intolerable toxicities, death, withdrawal of consent, initiation of new antitumor therapy, whichever occurred first.
Detailed Description
Bevacizumab biosimilar：7.5mg/kg，IV，D1，Q2W FOLFOX4： Oxaliplatin: 85 mg/m2 , IV, D1，Q2W Calcium leovorin: 200 mg/m2 ,IV, D1、D2，Q2W Fluorouracil: 400 mg/m2 push infusion and given 600mg/m2 intravenously 22 hours later， D1、D2, Q2W

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-orthotopic Liver Transplantation, Hepatocellular Carcinoma Recurrent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab combine with FOLFOX4
Arm Type
Experimental
Arm Description
Bevacizumab biosimilar：7.5mg/kg，IV，D1，Q2W FOLFOX4： Oxaliplatin: 85 mg/m2 , IV, D1，Q2W Calcium leovorin: 200 mg/m2 ,IV, D1、D2，Q2W Fluorouracil: 400 mg/m2 push infusion and given 600mg/m2 intravenously 22 hours later， D1、D2, Q2W Treatment will continue until disease progression, an unacceptable toxicity, or the patient voluntarily discontinues the study, whichever comes first.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab Biosimilar IBI305
Other Intervention Name(s)
FOLFOX4
Intervention Description
Patients received bevacizumab and FOLFOX4 every two weeks
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) ,Based on RECIST 1.1
Description
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Time Frame
From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years )
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS), Based on RECIST 1.1 and mRECIST
Description
PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on RECIST 1.1 and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
Time Frame
From the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) (up to approximately 2 years )
Title
Disease Control Rate (DCR) ,Based on RECIST 1.1 and mRECIST
Description
the proportion of patients who achieved CR, PR, or SD as their best overall response
Time Frame
Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit(up to approximately 2 years)
Title
Duration of Response (DOR) ,Based on RECIST 1.1 and mRECIST
Description
From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years)
Time Frame
DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 and mRECIST assessed by investigator analysis.
Title
Overall Survival (OS)
Description
From the date of first dose of study drug until date of death from any cause (up to approximately 2 years )
Time Frame
From the date of first dose of study drug until date of death from any cause (up to approximately 2 years )
Title
Time-to Response (TTR) Based on RECIST1.1 and mRECIST
Description
TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST1.1 and mRECIST assessed by investigate.
Time Frame
From date of first dose of study drug until CR or PR (up to approximately 2 years
Title
Objective Response Rate (ORR) ,Based on mRECIST
Description
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on mRECIST) assessed by investigator analysis.
Time Frame
From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years )
Title
Safety as measured by number and grade of adverse events
Description
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
From first dose until 30 days after the last dose (up to approximately 2 years )

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: adult patients with hepatocellular carcinoma who have received liver transplantation have postoperative radiographic or pathological evidence of recurrence; have not received the first line of standard treatment or have received the first line of standard treatment failure; at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 2; Child-Pugh class A or B (Child-Pugh score ≤7 ); adequate organ function; a predicted life expectancy of at least 3 months. Exclusion Criteria: allergy to the study drugs or their expedients or severe allergy to other monoclonal antibodies; receipt of attenuated inactivated vaccines within 4 weeks of the start of the study or scheduled for such vaccination during the study; evident concern of GI bleeding (local active ulcer, Guaic test at least ++) or a history of GI bleeding within the preceding 6 months; uncontrolled pleural or peritoneal effusion; pulmonary tuberculosis, sarcoidosis, HIV infection, or active HBV or HCV infection; uncontrolled cardiac arrhythmia (including QTC interval ≥500 ms); hepatic encephalopathy; Known hepatocholangiocarcinoma, mixed hepatocellular and cholangiocellular carcinoma, fibrolamellar carcinoma, or a history of or concurrent cancer except cervical carcinoma in situ and cured basal cell carcinoma; pregnant or lactating women or women contemplating pregnancy; severe concomitant illness that jeopardizes patient safety or interferes with the completion of the study as deemed by the investigators; esophageal or gastric variceal bleeding with portal hypertension within the past 6 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
yongxiang xia, doctor
Phone
86-025-68303211
Email
yx_xia@njmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
xuehao wang
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Study Chair
Facility Information:
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xuehao Wang
Phone
86-025-68303211
Email
wangxh@njmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Bevacizumab Biosimilar Plus FOLFOX4 in the Treatment of Recurrent HCC After Liver Transplantation

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