HAIC Combined With Sintilimab and Bevacizumab Biosimilar for Unresectable HCC

A Study to Evaluate the Efficacy and Safety of the Hepatic Arterial Infusion Chemotherapy(HAIC) Combined With Sintilimab and Bevacizumab Biosimilar in Unresectable Hepatocellular Carcinoma.

To Evaluate the Efficacy and Safety of the Hepatic Arterial Infusion Chemotherapy(HAIC) Combined With Sintilimab and Bevacizumab Biosimilar in the Treatment of Patients With Unresectable Hepatocellular Carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Drug: HAIC; Drug: Bevacizumab Biosimilar

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huikai Li, MD; Phone Number: 3091 862223340123; Email: lihuikai@tjmuch.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent should be signed before implementing any trial-related procedures;
• Age ranges from 18 to 75 years old.

• CNLC-IIb to IIIb HCC based on the Criteria for diagnosis and treatment of hepatocellular carcinoma (2019 edition)

  • At least ≥ 1 measurable lesions per mRECIST;
  • Child-Pugh grade A or B;
  • ECOG PS scores 0-1;
• No prior therapy for HCC.
• Expected survival time > 6 months;

• Sufficient organ functions, the subjects need to meet the following laboratory indicators:

  • 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 ≥1.5×10^9/L;Platelet count ≥ 100×10^9/L;Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN); or total bilirubin > ULN but direct bilirubin ≤ ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN;
  • Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥ 60 ml/min;
  • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN
  • Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, the subjects can also be included in the group in case total T3 (or FT3) and FT4 are within the normal range;
  • Myocardial enzyme spectrum should be within the normal range (if the investigator comprehensively judges that the simple laboratory abnormality is not clinically significant, the subject is also included);
• Female subjects of childbearing age should receive a urine or serum pregnancy test and the result is negative, 3 days prior to accept the first study drug administration (day 1 of cycle 1). In case the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Meanwhile, voluntary use of appropriate contraceptive methods shall be taken during the observation period and within 8 weeks of the last administration of the study drug; Women of non-bearing age are defined as at least 1 year after menopause, or those who have undergone surgical sterilization or hysterectomy; For males, appropriate contraceptive methods should be taken during the observation period and within 8 weeks after the last dose of the study drug.
• If there is a risk of pregnancy, all subjects (regardless of male and female) need to adopt contraceptives with an annual failure rate of less than 1% during the entire treatment period until 120 days after the last administration of the study drug (or 180 days after the last chemotherapeutic drug administration).

Exclusion Criteria:

• known as Inhibition of fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC；Previous HCC recurrence；Hepatic encephalopathy has been clinically diagnosed in the past 6 months .
• Autoimmune hepatitis (requiring liver puncture).
• History of organ transplantation or hepatic encephalopathy.
• Diffuse hepatoma.
• Clinical symptoms requiring drainage including pleural effusion, ascites, and pericardial effusion.
• History of nephropathy or nephrotic syndrome.
• Bleeding from a varicose vein in the esophagus or gastric fundus caused by portal hypertension in the past 6 months; Presence of severe (G3) varicose veins identified by endoscopy 3 months prior to initial administration; Evidence of portal hypertension (including imaging findings that the length of the spleen exceeds 10 cm and the platelets lower than 100), with a high risk of hemorrhage assessed by the investigator.
• Arteriovenous thromboembolic events in the past 6 months, including history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary artery embolism, deep vein thrombosis or any other serious thromboembolism. Implantable venous infusion port or catheter-derived thrombosis, or superficial venous thrombosis, except for those with stable thrombosis after conventional anticoagulation therapy.
• Severe bleeding tendency or coagulation dysfunction, or under thrombolytic therapy.
• Acceptance of preventive use of low-dose low-molecular-weight heparin (such as Enoxaparin 40 mg/day), except for vitamin K antagonists (such as warfarin).
• Requiring long-term medication for the inhibition of platelet function, such as aspirin, dipyridamole or clopidogrel.
• Uncontrollable hypertension, systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg after optimized medical treatment, history of critical hypertension or hypertensive encephalopathy.
• Symptomatic congestive heart failure (New York Heart Association class II-IV), symptomatic or poorly controlled arrhythmia, congenital long QT syndrome history or QTc > 500 ms corrected at screening (calculated using the Fridericia method).
• History of gastrointestinal perforation and or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea), Crohns disease, ulcerative colitis, or long-term chronic diarrhea in the past 6 months.
• Received major surgery (craniotomy, thoracotomy or laparotomy) or unhealed wounds, ulcers or fractures within 4 weeks prior to the first administration, except for received tissue biopsy or other minor surgery within 7 days prior to the first administration, venipuncture catheterization for intravenous infusion.
• Past and present history of lung diseases including pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, and severely impaired lung functions.
• Acute or chronic active hepatitis B or C infection.
• Active tuberculosis (TB), under anti-tuberculosis treatment or anti-tuberculosis treatment within 1 year prior to the first administration.
• Infected by human immunodeficiency virus (HIV) and known syphilis infection.
• Severe infections in active phase or poorly controlled clinically. Severe infection within 4 weeks prior to the first administration.
• Have used immunosuppressive drugs within 4 weeks before the first dose
• Received live attenuated vaccines within 4 weeks before the first dose or plan to receive live attenuated vaccines during the study period
• Received Chinese medicine with anti-tumor indications, or received drugs with immunomodulatory effect within 2 weeks before the first administration
• Received any anti-PD-1 antibody, anti-PD-L1/L2 antibody, anti-CTLA4 antibody, or other immunotherapy
• Allergic to Sintilizumab, Bevacizumab preparations and excipients, or had severe allergic reactions to other monoclonal antibodies in the past
• Received treatment from other clinical trials within 4 weeks before the first dose
• Female subjects who are pregnant or breastfeeding
• Other conditions that the subjects are not suitable to participate in this study according to the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Group; HAIC Combined With Sintilimab and Bevacizumab Biosimilar	Drug: Sintilimab; 200mg IV d1,Q3W; Other Names: IBI308; Drug: HAIC; hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment; Other Names: FOLFOX; Hepatic Artery Infusion Chemotherapy; Drug: Bevacizumab Biosimilar; 7.5mg/kg IV d1,Q3W; Other Names: IBI305

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate ( ORR)	Defined as proportion of patients who have a best response of CR or PR	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from the date of treatment start to the date of death	Up to 2 years
Events Free Survival (EFS)	Defined as the time from enrollment to disease progression, recurrence or death (whichever occurs first)	Up to 2 years
Surgical conversion rate	Defined as the incidence rate of patients that receive surgical resection.	Up to 2 years
R0 resection rate of patients who accepted surgical resection	Defined as the proportion of patients undergoing radical resection to the total patients accepted surgical resection	Up to 2 years
Pathological complete response (pCR) rate of patients who accepted surgical resection	Defined as the proportion of patients whose tumor and lymph node completely disappeared to the total patients accepted surgical resection	Up to 2 years
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 and complications of surgery	Up to 2 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 10, 2021
• Primary Completion (ACTUAL): January 10, 2022
• Study Completion (ANTICIPATED): November 10, 2023

Study Registration Dates

• First Submitted: August 29, 2021
• First Submitted That Met QC Criteria: August 29, 2021
• First Posted (ACTUAL): September 1, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Sintilimab; HAIC; Bevacizumab Biosimilar
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: HAICDD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No