Combination Therapy of HAIC, Sintilimab and Bevacizumab for Advanced Hepatocellular Carcinoma

Sponsor
Wuhan Union Hospital, China (Other)
Overall Status
Recruiting
CT.gov ID
NCT05617430
Collaborator
(none)
43
1
1
19
2.3

Study Details

Study Description

Brief Summary

This is a single-arm, exploratory study to evaluate the efficacy and safety of HAIC in combination with sintilimab and bevacizumab in the first line treatment of patients with BCLC-C hepatocellular carcinoma.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
43 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Exploratory Study to Evaluate the Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) Combine With Sintilimab and Bevacizumab for BCLC-C Hepatocellular Carcinoma
Actual Study Start Date :
Nov 2, 2022
Anticipated Primary Completion Date :
Apr 1, 2024
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: HAIC + Sintilimab + Bevacizumab

HAIC combine with Sintilimab and bevacizumab biosimilar

Drug: HAIC
Oxaliplatin: 85mg/m2 , Day 1 Leucovorin: 200mg/m2, Day 1 Fluorouracil: 400mg/m2, Day1 and 2400mg/m2 continuous arterial perfusion for 46h. Q3W
Other Names:
  • hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil, leucovorin (FOLFOX) treatment (Q3W)
  • Drug: Sintilimab
    200mg IV d1, Q3W
    Other Names:
  • IBI308
  • Drug: Bevacizumab Biosimilar IBI305
    7.5mg/kg IV d1, Q3W
    Other Names:
  • IBI305
  • Outcome Measures

    Primary Outcome Measures

    1. Progression free survival (PFS) per RECIST v1.1 [From baseline to primary completion date, about 18 months]

      Defined as a duration from the date of initial treatment to disease progression or death of any cause

    Secondary Outcome Measures

    1. The treatment-related adverse events (TRAEs) [From baseline to primary completion date, about 18 months]

      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

    2. Overall response rate (ORR) per RECIST v1.1 and mRECIST [From baseline to primary completion date, about 18 months]

      Defined as the incidence of complete response and, partial response

    3. Disease control rate (DCR) per RECIST v1.1 and mRECIST [From baseline to primary completion date, about 18 months]

      Defined as the incidence of complete response, partial response and stable disease

    4. Duration of response (DoR) per RECIST v1.1 and mRECIST [From baseline to primary completion date, about 18 months]

      Defined as a duration from date of initial treatment to disease progression or death in patients who achieve complete or partial response

    5. Overall survival (OS) [From baseline to primary completion date, about 18 months]

      Defined as a duration from the date of initial treatment to death of any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Written informed consent should be signed before implementing any trial-related procedures 2. ECOG PS scores 0-1 3. Histologically/cytologically confirmed HCC or cirrhosis meeting the clinical diagnostic criteria of HCC by American Association for the Study of Liver Diseases (AASLD) 4. Barcelona Clinic Liver Cancer (BCLC) stage C 5. Newly diagnosed HHC patients without any previous treatment for the tumor 6. Child Pugh score of ≤ 7. 7. Estimated survival > 12 weeks 8. At least one measurable lesion according to RECIST V1.1 9. Sufficient organ and bone marrow functions, with the laboratory test values within 7 days before the enrollment meeting the following requirements (no blood components, cell growth factors, albumin, and other drugs via intravenous or subcutaneous administrations are allowed for correction treatment within the first 14 days after the laboratory test results are obtained). The specific information is as follows:

    2. Routine blood test: absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 75 × 109/L; hemoglobin (HGB) ≥ 9.0 g/dL.

    3. Hepatic function: total bilirubin (TBIL) ≤ 3 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN; serum albumin ≥ 28 g/L; alkaline phosphatase (ALP) ≤ 5 × ULN.

    4. Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or clearance of creatinine (CCr) ≥ 50 mL/min (Cockcroft Gault formula); urinalysis results showing urine protein < 2+; patients whose baseline urinalysis results show urine protein ≥ 2+ should undergo 24 h urine collection and the 24 h urine protein quantitation test result should be lower than 1 g.

    5. Blood coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

    6. Female patients of childbearing age or male patients with female sexual partners of childbearing age should take effective contraceptive measures throughout the treatment and 6 months after the last dose.

    Exclusion Criteria:
    1. Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.

    2. History of hepatic encephalopathy or liver transplantation.

    3. Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage.

    4. Acute or chronic active hepatitis B or C infection; hepatitis B virus (HBV) DNA > 2000 IU/mL or 104 copies/mL; hepatitis C virus (HCV) RNA > 103 copies/mL; hepatitis B surface antigen (HbsAg) and anti HCV antibody positive concurrently.

    5. Presence of metastasis to the central nervous system.

    6. Presence of bleeding events from esophageal or gastric varices caused by portal hypertension within the past 6 months. Presence of known severe (G3) varicose veins in endoscopy within 3 months before the first dose. Evidence of portal hypertension (including the finding of splenomegaly in imaging studies) with a high risk of bleeding assessed by the investigator.

    7. Presence of any life-threatening bleeding events within the past 3 months, including the need for transfusion, surgery or local treatment, and continuous medication therapy.

    8. Any arterial/venous thromboembolic events within 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of serious thromboembolism. Presence of implantable venous port or catheter derived thrombosis, or superficial venous thrombosis, barring stable thrombosis following the conventional anticoagulation treatment. Prophylactic use of low dose low molecular weight heparin (e.g., enoxaparin 40 mg/day) is permitted.

    9. Involvement of both the main portal vein and the left and right branches by portal vein tumor thrombus, or of both the main trunk and the superior mesenteric vein concurrently. Presence of tumor thrombus of inferior vena cava.

    10. A 10-day consecutive dosing of aspirin (> 325 mg/day) or other drugs, e.g., dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeks before the first dose.

    11. Uncontrolled hypertension (systolic greater than 140 mmHg or diastolic greater than 90 mmHg) after the optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.

    12. Toxicity (excluding alopecia, events not clinically significant, and asymptomatic laboratory abnormalities) caused by previous therapy that has not yet resolved to grade 0 or 1 (National Cancer Institute Common Terminology Criteria for Adverse Events V5.0 (NCI CTCAE V5.0)) before the first dose of study drugs.

    13. Symptomatic congestive cardiac failure (NYHA Class II IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500 ms (calculated using Fridericia formula) during screening.

    14. Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic therapy.

    15. History of gastrointestinal perforation and/or fistula, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection accompanied with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months.

    16. Receipt of immunosuppressants within 4 weeks before the first dose, excluding local glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or equivalents), while the temporary use of glucocorticoids for preventing allergies or treating dyspneic symptoms of such diseases as asthma and chronic obstructive pulmonary disease is permitted.

    17. Receipt of a live attenuated vaccine within 4 weeks before the first dose or planned to receive a live attenuated vaccine during the study.

    18. Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of tissue biopsy or other minor surgeries within 7 days before the first dose, barring venipuncture and catheterization for intravenous infusion.

    19. Receipt of local treatment for liver cancer within 4 weeks before the first dose.

    20. Receipt of systemic treatment with traditional Chinese medicines with cancer indications or immunomodulators (including thymosin, interferon, and interleukin, barring local use for controlling pleural fluid or ascites) within 2 weeks before the first dose.

    21. Uncontrolled/uncorrectable metabolic disorders, other non malignant organ diseases, systemic diseases, or cancer related secondary diseases with the potential to cause a relatively high medical risk and/or survival evaluation uncertainties unsuitable for subject enrollment as judged by the investigator; other circumstances unsuitable for subject enrollment as judged by the investigator.

    22. Other malignancies diagnosed within 5 years before the first dose, excluding radically treated basal cell carcinoma of skin, squamous cell carcinoma of skin, and/or radically resected carcinoma in situ. If other malignancies were diagnosed over 5 years pre dose, the liver lesions should still be subjected to pathological or cytological diagnosis even if they meet the clinical diagnostic criteria for HCC by AASLD; individuals with confirmed HCC can be enrolled.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China

    Sponsors and Collaborators

    • Wuhan Union Hospital, China

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Wuhan Union Hospital, China
    ClinicalTrials.gov Identifier:
    NCT05617430
    Other Study ID Numbers:
    • UHCT22623
    First Posted:
    Nov 15, 2022
    Last Update Posted:
    Nov 15, 2022
    Last Verified:
    Nov 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 15, 2022