Hepatocellular carcinoma
Conditions
Interventions
combination group:Pirfenidone Combination Therapy Following Failure of First-line Lenvatinib-containing Regimen
Sponsors
The Third Affiliated Hospital of Naval Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Gender is not limited, age 18-75 years old; 2. Hepatocellular carcinoma diagnosed clinically, pathologically, or cytologically; 3. The first-line regimen contains clear progress on imaging after treatment with lenvatinib; 4. The subject or guardian understands and voluntarily signs the informed consent form, and has the willingness and ability to complete the regular visits, treatment plans, laboratory tests, etc. required by the program; 5. Subjects are not suitable for radical resection, transplantation or ablation, including recurrence after radical resection and are not suitable for recurrent radical resection or ablation; 6. Estimated survival time of more than 12 weeks; 7. Have not received radiotherapy within 12 weeks before the first dose; 8. Child-Pugh grade A or grade B with a score of 7 in liver function; 9. ECOG score is 0-1 points; 10. Have adequate organ and bone marrow function, and the laboratory test values within 7 days before enrollment meet the following requirements (within 14 days before obtaining laboratory tests, it is not allowed to meet the conditions by giving any blood components, cell growth factors, albumin and other corrective treatment drugs), as follows: 1) Routine blood count: absolute neutrophil count (ANC) >=1.5×10^9/L; platelet count (PLT) >=75×10^9/L; hemoglobin (HGB) >=9.0 g/dL; 2) Liver function: serum total bilirubin (TBIL) =28 g/L; 3) renal function: serum creatinine (Cr) = 50mL/min (Cockcroft-Gault formula); For patients with urine protein ><=2+ on urine routine at baseline, 24-hour urine collection should be performed and 24-hour urine protein quantification should be <1 g. 4) Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) < = 1.5 times ULN 11. For female subjects of childbearing age, a urine or serum pregnancy test should be received within 3 days before receiving the first dose of study drug (Cycle 1 Day 1) with a negative result. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is requested. and voluntarily use an adequate method of contraception during the observation period and for 8 weeks after the last dose of study drug; Females of non-childbearing potential are defined as at least 1 year postmenopausal, or have undergone surgical sterilization or hysterectomy; For males, an adequate method of contraception should be used during the observation period and for 8 weeks after the last dose of study drug; 12. If there is a risk of conception, all subjects (regardless of male or female) are required to use contraception with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy drug).
Exclusion criteria
Exclusion criteria: 1.Uncorrectable coagulopathy with significant bleeding tendency. 2.Exclusion of target diseases: Mixed hepatocellular carcinoma and cholangiocarcinoma; evidence of coexisting malignancies. 3.Diagnosis of other malignancies within 3 years prior to the first dose (excluding radically treated basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, and/or carcinoma in situ with curative resection). 4.Patients requiring long-term anticoagulant or antiplatelet therapy who are unable to discontinue medication. 5.Patients with hepatic encephalopathy or refractory ascites/pleural effusion requiring therapeutic intervention. 6.Recent antitumor or systemic therapies: Use of herbal medicines with confirmed antitumor activity within 2 weeks prior to enrollment; administration of herbal medicines with antitumor indications or immunomodulatory agents (e.g., thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks. 7.Systemic treatment: Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal/pituitary insufficiency) are not considered systemic therapy. Systemic corticosteroids (>10 mg/day prednisone or equivalent) or immunosuppressive therapy within 7 days prior to the first dose, excluding topical (nasal, inhaled, or local) corticosteroids. 8.Severe hepatic or renal insufficiency. 9.Severe or uncontrolled systemic diseases, including: Symptomatic, clinically significant ECG abnormalities (e.g., complete left bundle branch block, second-/third-degree heart block, ventricular arrhythmias, atrial fibrillation). Unstable angina, congestive heart failure (NYHA class >=2), or myocardial infarction within 6 months prior to randomization. Esophageal/gastric variceal bleeding within 6 months. Poorly controlled hypertension (systolic >140 mmHg, diastolic >90 mmHg). History of non-infectious pneumonitis requiring corticosteroids within 1 year or active interstitial lung disease. Active tuberculosis; uncontrolled systemic infection requiring therapy. Active diverticulitis, abdominal abscess, or gastrointestinal obstruction. Hepatic disorders (e.g., cirrhosis, decompensated liver disease, acute/chronic active hepatitis). Active ulcers or gastrointestinal bleeding. Poorly controlled diabetes (fasting blood glucose >10 mmol/L). Urine protein >=++ with 24-hour urinary protein >1.0 g. Uncontrolled hypercalcemia (ionized calcium >1.5 mmol/L, total calcium >12 mg/dL, or corrected serum calcium exceeding ULN) or symptomatic hypercalcemia requiring bisphosphonates. Non-healing wounds or fractures. Psychiatric disorders impairing protocol compliance. 10.Pregnant or lactating females. 11.Investigator-determined inability or unwillingness to adhere to the study protocol. 12.Hypersensitivity to the investigational drug(s).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression-free survival;objective response rate;safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| overall survival;disease control rate;duration of response; | — |
Countries
China
Contacts
Public ContactYuan Shengxian/Zhou Weiping
The Third Affiliated Hospital of Naval Medical University
Outcome results
None listed