Sintilimab Combined With Bevacizumab Biosimilar for Potentially Resectable Intermediate HCC

NCT04843943 | Unknown Phase 1

• 1 other identifier: B2020-156(2)R
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase Ib study to evaluate the safety and efficacy of sintilimab combined with bevacizumab biosimilar in patients with potentially resectable intermediate hepatocellular carcinoma (HCC).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Adverse Events (AEs)

  Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0; Surgical safety including Intraoperative blood loss，PHLF assessed by ISGLS（2012），Postoperative complications evaluated by modified Clavien-Dindo system

  Up to 2 years

• Events Free Survival (EFS) Assessed by RECIST1.1

  Defined as the time from enrollment to disease progression, recurrence or death (whichever occurs first)

  Up to 2 years

Secondary Outcomes (8)

• resection rate (R0 resection rate)

  Up to 2 years

• Pathological response rate

  Up to 2 years

• Objective response rate (ORR) assessed by RECIST1.1

  Up to 2 years

• Recurrence-free survival (RFS) of patients who accepted surgery

  Up to 2 years

• Progression free survival (PFS) assessed by RECIST1.1 of patients who didn't accept surgery

  Up to 2 years

Study Arms (1)

Sintilimab+Bevacizumab

EXPERIMENTAL

Drug: Sintilimab; Drug: Bevacizumab Biosimilar

Interventions

Sintilimab DRUG

Sintilimab: 200mg IV Q3W D1

Sintilimab+Bevacizumab

Bevacizumab Biosimilar DRUG

Bevacizumab biosimilar: 15mg/kg, IV, Q3W, D1

Sintilimab+Bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent and willing to sign an approved consent form
• Age 18-75, male and female
• Potentially resectable Intermediate (CNLC-IIa and IIb) HCC with diagnosis confirmed by histology/cytology or clinically
• No prior therapy for HCC
• Child-Pugh: A
• ECOG PS: 0-1
• Expected survival ≥6 months
• Measurable disease per RECIST1.1
• Major organ functions meet the following requirements:
• no blood transfusion, no use of hematopoietic stimulators (including g-csf, gm-csf, EPO and TPO) and infusion of human albumin preparations within 14 days prior to screening: neutrophil absolute count ≥1.0×10\^9/L;Platelet count ≥ 75×10\^9/L;Hemoglobin ≥ 9 g/dL;Serum albumin ≥ 2.8 g/dL;Total serum bilirubin ≤2.0× upper limit of normal range (ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN;Serum creatinine (Cr) ≤1.5×ULN or Cr clearance ≥30 mL/min (calculated by Cockcroft-Gault formula);International standardized ratio (INR) ≤1.5×ULN;
• Women of childbearing age must undergo a blood pregnancy test within the first 3 days of randomization with negative results and agree to use a reliable and effective method of contraception during the trial and within 120 days of the last trial drug administration. Male patients whose partners are women of childbearing age must agree to use a reliable and effective method of contraception during the trial and within 120 days of the last trial drug administration.

You may not qualify if:

• known as cholangiocarcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and hepatic fibrolamellar carcinoma.
• History of organ transplantation or hepatic encephalopathy
• Tumor accumulation range exceeds 70% of liver volume
• Pleural fluid, ascites, and pericardial effusion with clinical symptoms requiring drainage
• Any history of kidney disease or nephrotic syndrome
• History of gastrointestinal (GI) perforation and/or fistula in the past 6 months;Severe (G3) varicose veins are known to be present on endoscopy within 3 months before the first dose ; history of thrombosis, bleeding diathesis, coagulopathy or significant vascular disease
• Prior life-threatening blood loss or grade 3/4 gastrointestinal bleeding requiring blood infusion, endoscopic or surgical intervention within 3 months
• Arterial and venous thromboembolic events in the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious thromboembolism history.
• Severe bleeding tendency or coagulopathy, or are receiving thrombolytic therapy
• Long-term use of vitamin K antagonists (such as warfarin) or low-dose low-molecular-weight heparin (such as enoxaparin 40 mg/day) or heparin
• Uncontrollable hypertension, systolic blood pressure\> 140 mmHg or diastolic blood pressure\> 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy
• Symptomatic congestive heart failure (New York Heart Association Grade II-IV), symptomatic or poorly controlled arrhythmia, history of congenital long QT syndrome or QTc\> 500ms corrected during screening
• History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months of initiation of study treatment
• Had major surgical procedure within 4 weeks of initiation of study treatment
• Past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases

Sponsors & Collaborators

• Fudan University: lead

Related Publications (1)

• Sun HC, Zhu XD, Wang ZY, Gao Q, Ji Y, Shi YH, Wang XY, Qiu SJ, Huang C, Shen YH, Zhou J, Fan J. Sintilimab plus bevacizumab followed by resection in intermediate-stage hepatocellular carcinoma: a phase Ib clinical trial with biomarker analysis. BMJ Oncol. 2024 Dec 16;3(1):e000578. doi: 10.1136/bmjonc-2024-000578. eCollection 2024.

  PMID: 40046248 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab

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

Central Study Contacts

Huichuan Sun

CONTACT

13701922065; sun.huichuan@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of hospital

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 14, 2021
• Study Start: May 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2023
• Last Updated: April 14, 2021

Record last verified: 2021-04