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

The First Affiliated Hospital with Nanjing Medical University15 enrolled

Overview

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.

Bevacizumab biosimilar：7.5mg/kg，IV，D1，Q2W FOLFOX4： 1. Oxaliplatin: 85 mg/m2 , IV, D1，Q2W 2. Calcium leovorin: 200 mg/m2 ,IV, D1、D2，Q2W 3. Fluorouracil: 400 mg/m2 push infusion and given 600mg/m2 intravenously 22 hours later， D1、D2, Q2W

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Post-orthotopic Liver Transplantation Hepatocellular Carcinoma Recurrent

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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 Outcomes

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).

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 )

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

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)

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)

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.

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 frame: 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.

Time frame: From date of first dose of study drug until CR or PR (up to approximately 2 years

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.

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 )

Safety as measured by number and grade of adverse events

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 )