Chidamide Combined With Sintilimab and Bevacizumab for the First-line Treatment of Advanced Liver Cancer

NCT06408623 | Not Yet Recruiting Phase 2

• 1 other identifier: CSIIT-Q75
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to explore the safety and tolerability of chidamide in combination with Sintilimab and bevacizumab in patients with advanced liver cancer, to determine the recommended dose for this combination regimen, and to explore preliminary efficacy data. And based on the tumor immune microenvironment multidimensional (lymphocyte subsets, multiple cytokines, multicolor fluorescence immunohistochemistry, single cell sequencing, etc.) to explore the therapeutic efficacy related markers.

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  progression free surival

  24 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Drug: chidamide combined with Sintilimab and bevacizumab

Interventions

chidamide combined with Sintilimab and bevacizumab DRUG

chidamide combined with Sintilimab and bevacizumab

Treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years old and ≤75 years old, regardless of gender;
• \. Hepatocellular carcinoma confirmed by histology or cytology;
• \. Have not received any previous systematic therapy for HCC;
• \. Barcelona (BCLC) has stage B-C and is not suitable for surgical local treatment, or progresses after surgery and/or local treatment;
• \. Child-Pugh liver function grade A and good grade B (≤7 points)
• \. ECOG score 0-1;
• \. Have at least one measurable lesion (according to RECIST v1.1 assessment criteria);
• \. Expected survival time ≥3 months;
• \. The functional level of vital organs must meet the requirements before the first use of the experimental drug; (1) Blood system function (no blood transfusion and no cell growth factor correction within 14 days before screening) : neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, hemoglobin ≥ 90 g/L; (2) Liver and kidney function (no albumin infusion within 14 days before screening) : serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN), serum albumin ≥ 29 g/L, ALT and AST ≤ 2.5×ULN; Serum creatinine ≤1.5×ULN or endogenous creatinine clearance (Cockcroft-Gault formula) ≥60ml/min; (3) Coagulation function: International standardized ratio (INR) ≤1.5 or prothrombin time (PT) exceeding the normal control range ≤6 seconds; (4) Left ventricular ejection fraction (LVEF) ≥ 50% by two-dimensional echocardiography;
• \. Subjects (both female and male) agree to use effective contraceptive methods for contraception from the date of signing the informed consent to 180 days after the last use of the experimental drug. A woman of childbearing age cannot be pregnant or lactating;
• \. Patients with active hepatitis B infection who had HBV DNA\<2000 IU/ml during the 28 days prior to study entry and who were receiving treatment and taking stable doses of antiviral drugs for at least 7 days upon study entry;
• \. Any acute, clinically significant treaty-related toxicity must be restored to ≤ grade 1 (according to CTCAE v5.0) prior to initial use of the investigational drug, except for hair loss;
• \. Voluntarily participate in this clinical trial and sign a written informed consent.

You may not qualify if:

• \. Imaging examination showed that large intrahepatic hemangioma thrombus was complicated (including synchronous thrombus of main portal vein and left and right branches, synchronous thrombus of main portal vein and superior mesenteric vein, and inferior vena cava thrombus);
• \. Patients who had clinically uncontrollable pleural effusion, peritoneal effusion, pericardial effusion, etc. before receiving the study for the first time and could not be enrolled by the researchers. ;
• \. Patients with a history of other malignancies within 5 years prior to signing informed consent (except cured basal cell skin cancer, skin squamous cell carcinoma, and/or carcinoma in situ after radical resection)
• \. Active autoimmune disease that may worsen in the course of receiving investigational drug therapy
• \. In the judgment of the investigator, there are conconitant diseases that seriously threaten the safety of the subjects or affect the completion of the study, such as hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg) that cannot be controlled by two or more antihypertensive drugs, and diabetes that is not well controlled;
• \. History of hypertensive crisis or hypertensive encephalopathy
• \. The presence of disease requiring systemic treatment with corticosteroids (\>10 mg daily or equivalent of prednisone) or other immunosuppressive agents within 2 weeks prior to initial study treatment
• \. History of allogeneic hematopoietic stem cell transplantation or organ transplantation (except corneal transplantation)
• \. Systemic infections or other serious infections requiring intravenous antibiotic treatment \>7 days within 2 weeks prior to first use of the experimental drug
• \. HIV positive; HCV antibody positive and HCV RNA positive \[Note: if the HCV RNA test result is negative, it can be considered not infected with HCV\]; Patients with co-infection of HBV and HCV
• \. People who are known to have received anti-tuberculosis therapy within one year prior to first receiving study therapy
• \. Subjects with any of the following cardiovascular diseases were excluded: a) acute myocardial infarction occurred within 6 months prior to first administration of the investigational drug. b) Past and/or current New York Heart Association Class III or IV heart failure. c) Currently has poorly controlled cardiovascular disease, including angina, pulmonary hypertension, or severe heart rhythm or conduction abnormalities. d) Prior to first administration of the trial drug, the 12-lead ECG showed an average QT interval (QTcF) of \>450 ms (male) or \>470 ms (female).
• \. The patient is known to have a history of psychotropic substance abuse, alcohol abuse or drug use; A clear history of neurological or psychiatric disorders, including epilepsy or dementia or hepatic encephalopathy.
• \. People who have participated in other clinical studies and used other clinical trial drugs within 4 weeks before using the experimental drug.
• \. Previously received immunotherapy, including immune checkpoint inhibitory antibodies (such as anti-PD-1, PD-L1, CTLA-4 antibodies, etc.), immune checkpoint activating antibodies (such as: Anti-icos, CD40, CD137, GITR, OX40 antibody, etc.), and immune cell therapy, or have previously received anti-VEGF, VEGFR targeted therapy or HDACi therapy.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Liver Neoplasms

Interventions

sintilimab; Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice director of Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 10, 2024
• Study Start: May 15, 2024
• Primary Completion: May 15, 2025
• Study Completion: May 15, 2026
• Last Updated: May 10, 2024

Record last verified: 2024-05