Sintilimab Combined With Bevacizumab Biosimilar for Potentially Resectable Intermediate HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

An Exploratory Study of Sintilimab in Combination With Bevacizumab Biosimilar in Patients With Potentially Resectable Intermediate HCC

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04843943
• Other study ID #: B2020-156(2)R
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 1, 2021
• Est. completion date: May 1, 2023

Study information

• Verified date: April 2021
• Source: Fudan University
• Contact: Huichuan Sun
• Phone: 13701922065
• Email: sun.huichuan[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Able to provide informed consent and willing to sign an approved consent form

2. Age 18-75, male and female

3. Potentially resectable Intermediate (CNLC-IIa and IIb) HCC with diagnosis confirmed by histology/cytology or clinically

4. No prior therapy for HCC

5. Child-Pugh: A

6. ECOG PS: 0-1

7. Expected survival =6 months

8. Measurable disease per RECIST1.1

9. 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;

10. 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.

Exclusion Criteria:

1. known as cholangiocarcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and hepatic fibrolamellar carcinoma.

2. History of organ transplantation or hepatic encephalopathy

3. Tumor accumulation range exceeds 70% of liver volume

4. Pleural fluid, ascites, and pericardial effusion with clinical symptoms requiring drainage

5. Any history of kidney disease or nephrotic syndrome

6. 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

7. Prior life-threatening blood loss or grade 3/4 gastrointestinal bleeding requiring blood infusion, endoscopic or surgical intervention within 3 months

8. 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.

9. Severe bleeding tendency or coagulopathy, or are receiving thrombolytic therapy

10. 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

11. Uncontrollable hypertension, systolic blood pressure> 140 mmHg or diastolic blood pressure> 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy

12. 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

13. History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months of initiation of study treatment

14. Had major surgical procedure within 4 weeks of initiation of study treatment

15. Past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases

16. Had acute or chronic active hepatitis B or C infection. Hepatitis C virus (HCV) RNA>103 copies/ml; hepatitis B surface antigen (HbsAg) and anti-HCV antibody are positive at the same time; hepatitis B virus (HBV) DNA positive but has received antiviral treatment is allowed.

17. Had active tuberculosis (TB)

18. Had human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive), known syphilis infection

19. Had severe infections that are active or poorly clinically controlled.

20. Had active autoimmune disease

21. Have used immunosuppressive drugs within 4 weeks before the first dose

22. Received live attenuated vaccines within 4 weeks before the first dose or plan to receive live attenuated vaccines during the study period

23. Received Chinese medicine with anti-tumor indications, or received drugs with immunomodulatory effect within 2 weeks before the first administration

24. Received any anti-PD-1 antibody, anti-PD-L1/L2 antibody, anti-CTLA4 antibody, or other immunotherapy

25. Allergic to Sintilizumab, Bevacizumab preparations and excipients, or had severe allergic reactions to other monoclonal antibodies in the past

26. Received treatment from other clinical trials within 4 weeks before the first dose

27. Female patients who are pregnant or breastfeeding

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Sintilimab
Sintilimab: 200mg IV Q3W D1
• Bevacizumab Biosimilar
Bevacizumab biosimilar: 15mg/kg, IV, Q3W, D1

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	resection rate (R0 resection rate)	Defined as the proportion of patients undergoing radical resection to the total subjects (R0 resection rate)	Up to 2 years
Secondary	Pathological response rate	Defined as the proportion of patients who had pathological response.	Up to 2 years
Secondary	Objective response rate (ORR) assessed by RECIST1.1	Defined as the proportion of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).	Up to 2 years
Secondary	Recurrence-free survival (RFS) of patients who accepted surgery	Defined as the time from the date of surgery to the date of disease recurrence or death whichever occur first, assessed up to 2 years post-treatment	Up to 2 years
Secondary	Progression free survival (PFS) assessed by RECIST1.1 of patients who didn't accept surgery	Defined as the time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.	Up to 2 years
Secondary	Overall survival (OS) of the patients who accepted surgery	Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive.	Up to 2 years
Secondary	Overall survival (OS) of the patients who didn't accepted surgery	Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive.	Up to 2 years
Secondary	Overall survival (OS)	Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive	Up to 2 years