HAIC Combined With Cadonilimab and Bevacizumab as First-line Therapy in Unresectable Hepatocellular Carcinoma

Hepatic Arterial Infusion of Oxaliplatin Plus Fluorouracil/Leucovorin Combined With Cadonilimab and Bevacizumab as First-line Therapy in Unresectable Hepatocellular Carcinoma: a Single Center, Open Label, Single Arm,, Phase II Trial

To evaluate the efficacy and safety of HAIC combined with Cadonilimab and bevacizumab as first-line therapy in Unresectable hepatocellular carcinoma

Study Overview

• Status: Not yet recruiting
• Conditions: Unrescetable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: HAIC+Cadonilimab+Bevacizumab

Detailed Description

An open label, single-arm, single center, phase II study evaluating HAIC combined with cadonilimab and bevacizumab as first-line therapy in unresectable hepatocellular carcinoma

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

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300308
      • Tianjin Cancer Hospital Airport Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. written informed consent signed prior to enrolment.
2. age 18-75 years, both sexes.
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. ECOG PS of 0 or 1.
5. Absence of systemic anti-tumor treatment for HCC before the first dose.
6. Barcelona Clinic Liver Cancer (BCLC) stage of C. Stage B for those unsuitable for radical surgery and/or local treatment.
7. At least one measurable lesion according to RECIST V1.1, or measurable lesions showing definite progression following the local treatment based on RECIST V1.1.
8. Child-Pugh score of ≤ 7.
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:

1) Routine blood test: absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 75 × 10^9/L; hemoglobin (HGB) ≥ 9.0 g/dL.

2) Hepatic function: total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN; serum albumin ≥ 28 g/L; alkaline phosphatase (ALP) ≤ 5 × ULN. 3) 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 24-h urine protein quantitation test result should be < 1 g.

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

10.Estimated survival ≥ 12 weeks. 11. 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. Those who possess the indicators lower than the above criteria after nucleotide antiviral treatment can be enrolled.
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 vein 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. 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.
9. 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.
10. History or current experience of pulmonary fibrosis and such lung diseases as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, and severely impaired lung function.
11. 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.
12. Previous receipt of any antibody treatment involving anti-PD-1, anti-PD-L1/L2, or anti-CTLA4 or other immunotherapies. Previous receipt of anti-VEGF and/or VEGFR, RAF, MEK, PDGFR, and FGFR targeted therapy.
13. Pregnant or breastfeeding female patients.
14. lead to the following consequences: increased study participation or drug-related risks, or interference with interpreting trial results, and considered ineligible for participating in the trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC+cadonilimab+bev	Drug: HAIC+Cadonilimab+Bevacizumab; Cadonilimab: 10mg/kg, iv,q3w Bevacizumab: 7.5mg/kg, iv, q3w HAIC: Oxaliplatin plus Fluorouracil/Leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate ( ORR) per RECIST 1.1	Defined as proportion of patients who have a best response of CR or PR	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from enrollment to death from any cause	Up to two 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	Up to two years
Progress Free Survival (PFS)	Defined as the time from enrollment to disease progression or death (whichever occurs first)	Up to two years
Disease Control Rate (DCR) per RECIST 1.1	Defined as proportion of patients who have CR or PR or SD	Up to 1 year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2023
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• 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: AK104-IIT-C-N-0052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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