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

NCT05617430 | Unknown Phase 2

• 1 other identifier: UHCT22623
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) per RECIST v1.1

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

  From baseline to primary completion date, about 18 months

Secondary Outcomes (5)

• The treatment-related adverse events (TRAEs)

  From baseline to primary completion date, about 18 months

• Overall response rate (ORR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• Disease control rate (DCR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• Duration of response (DoR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• Overall survival (OS)

  From baseline to primary completion date, about 18 months

Study Arms (1)

HAIC + Sintilimab + Bevacizumab

EXPERIMENTAL

HAIC combine with Sintilimab and bevacizumab biosimilar

Drug: HAIC; Drug: Sintilimab; Drug: Bevacizumab Biosimilar IBI305

Interventions

HAIC DRUG

Oxaliplatin: 85mg/m2 , Day 1 Leucovorin: 200mg/m2, Day 1 Fluorouracil: 400mg/m2, Day1 and 2400mg/m2 continuous arterial perfusion for 46h. Q3W

Also known as: hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil, leucovorin (FOLFOX) treatment (Q3W)

HAIC + Sintilimab + Bevacizumab

Sintilimab DRUG

200mg IV d1, Q3W

Also known as: IBI308

HAIC + Sintilimab + Bevacizumab

Bevacizumab Biosimilar IBI305 DRUG

7.5mg/kg IV d1, Q3W

Also known as: IBI305

HAIC + Sintilimab + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• \. 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:
• Routine blood test: absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 75 × 109/L; hemoglobin (HGB) ≥ 9.0 g/dL.
• 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.
• 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.
• Blood coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• \. 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.

You may not qualify if:

• Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
• History of hepatic encephalopathy or liver transplantation.
• Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage.
• 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.
• Presence of metastasis to the central nervous system.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic therapy.
• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Folfox protocol; Therapeutics; 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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Central Study Contacts

Bin Liang

CONTACT

86-18086006235; 553954881@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 15, 2022
• Study Start: November 2, 2022
• Primary Completion: April 1, 2024
• Study Completion: June 1, 2024
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)