Prospective registration

A multicenter, prospective, Exploratory research study of modified DEB-TACE in the treatment of unresectable large liver cancer in Shandong

A multicenter, prospective, Exploratory research study of modified DEB-TACE in the treatment of unresectable large liver cancer in Shandong

Zhu Guangxiao 

Yu Guangji 

Luo Yuan Da Jie Xiang Heng Plaza, Lixia District, Jinan City, Shandong Province

Linyi Cancer Hospital, No. 6, Lingyuan East Street, Linyi City, Shandong Province

Jiangsu Jiangsu Hengrui Medicine Co., Ltd

Linyi Cancer Hospital

Yes

Ethics Committee of Linyi Cancer Hospital

Chen fei

Intersection of Zhongyi Street and Zhicheng Road, Hedong District, Linyi City

Linyi Cancer Hospital

Linyi Cancer Hospital, No. 6, Lingyuan East Street, Linyi City, Shandong Province

raise independently

Hepatocellular carcinoma

Interventional study

4

Single arm 

Evaluate the effectiveness of modified DEB-TACE in treating unresectable large blood supply liver cancer patients by evaluating objective response rate (ORR)

1. Voluntarily participate in this study and sign an informed consent form. 2. Age ≥ 18 years old, both male and female. 3. Subjects diagnosed with HCC through histopathology/cytology or clinically diagnosed with HCC according to the "Diagnosis and Treatment Guidelines for Primary Liver Cancer (2022 Edition)". 4. Subjects confirmed by histopathology must be able to provide fresh or archived tumor tissues (Formaldehyde#Forms fixed, paraffin embedded [FFPE] tissue blocks or at least 3 unstained FFPE slides) and their pathological reports; If the subject is able to provide less than 3 unstained slides or the tumor tissue is not available (for example, due to previous diagnostic tests being exhausted), after discussing each case with the medical supervisor, admission may be allowed based on the specific situation. 5. CNLC staging: Stage IB-IIIB (BCLC staging B or C), with a tumor diameter greater than 7cm. 6. Child Pugh liver function rating within 7 days before enrollment: A or B (≤ 7 points). 7. ECOG PS score within 7 days before enrollment: 0-1 points. 8. I have not received systematic anti-tumor treatment for hepatocellular carcinoma in the past. 9. Evaluated by researchers as suitable for TACE treatment. 10. Subjects who have previously undergone radical surgery or ablation are allowed to undergo a preventive TACE after surgery. 11. Expected survival time ≥ 12 weeks. 12. The main organ functions meet the following requirements (within 7 days before enrollment): (1) Routine blood examination: (excluding hemoglobin, no blood transfusion, no use of granulocyte Colony-stimulating factor [G-CSF], no use of drugs for correction within 14 days before screening): Absolute neutrophil count ≥ 1.5 × 10 ^ 9/L; Platelets ≥ 50 × 10 ^ 9/L; Hemoglobin ≥ 90g/L. (Leukocyte and thrombocytopenia caused by hypersplenism can be included after partial embolization of the splenic artery or medication correction) (2) Blood biochemical examination (no albumin transfusion within 14 days before screening): Serum albumin ≥ 28g/L; Total serum bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; Blood creatinine ≤ 1.5 × ULN or Cr clearance rate>50ml/min (Cockcroft Fault formula is as follows): Male: Cr clearance rate=(140 age) × Weight)/(72 × Blood Cr) Female: Cr clearance rate=(140 age) × Weight)/(72 × Blood Cr) × zero point eight five Body weight unit: kg; Blood Cr unit: mg/ml; (3) International standardized ratio (INR) ≤ 2.3 or Prothrombin time (PT) exceeds the range of normal control ≤ 6 seconds; (4) Urinary protein<2+(If urinary protein ≥ 2+, 24-hour urine protein quantification is required, and 24-hour urine protein quantification<1.0g can be included in the group). 13. If you have hepatitis B virus (HBV) infection, the HBV DNA must be<2000IU/mL (if the research center has only copy/mL detection unit, it must be<10000copy/mL), and you are willing to receive antiviral treatment throughout the study period (treatment according to the diagnostic and treatment guidelines, such as Entecavir) and regular monitoring; Hepatitis C virus (HCV) ribonucleic acid (RNA) positive subjects must receive antiviral treatment according to diagnostic and treatment guidelines, and their liver function must be within CTCAE1 level elevation. 14. Subjects with esophageal and gastric varices need to be evaluated or treated before enrollment. 15. Women with Fertility: must agree to contraception from signing the informed consent form to 6 months after the last TACE treatment or 90 days after the last administration of the study drug (whichever is longer). And the blood HCG test must be negative within 7 days before starting the study treatment; And it must be non lactating. 16. If the female subject has menstruated, has not reached the post menopausal state, and has not undergone sterilization surgery (such as Hysterectomy, bilateral Tubal ligation or bilateral oophorectomy), it is considered that the subject has Fertility. 17. For male subjects whose partners are women with Fertility, they must agree to abstain from sex from signing the informed consent form until 6 months after the last TACE treatment or 90 days after the last administration of the study drug (whichever is longer), or use reliable and effective methods of contraception. Male participants must also agree not to donate sperm during the same time period. Male participants whose partners are already pregnant must use condoms and do not need to use other contraceptive methods.

1. Known hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma of liver and fibrolamellar cell carcinoma; Within 5 years or simultaneously suffering from other active malignant tumors other than hepatocellular carcinoma. Cured local tumors, such as skin Basal-cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate Carcinoma in situ, cervical Carcinoma in situ, breast Carcinoma in situ, can be included in the group. 2. Vp4 portal vein invasion (Vp classification by the Japanese Society for Liver Cancer Research). 3. There is uncontrollable extrahepatic metastasis, such as lung and brain metastasis (EHS). 4. Intrahepatic lesions account for ≥ 70% of the liver volume. 5. At present, it is suitable for patients undergoing radical Sex therapy such as surgical resection, ablation or transplantation. 6. Previously received local treatment, including therapeutic TACE, transarterial embolization (TAE), hepatic artery infusion chemotherapy (HAIC), and transarterial radiation embolization (TARE). a) Note: Subjects who have previously received radical local treatment (such as ethanol injection (PEI) or radiation therapy) are allowed to be included in the group, but lesions treated locally cannot be used as target lesions. 7. Subjects who are preparing to undergo or have previously received organ or allogeneic bone marrow transplantation. 8. People with interstitial pneumonia or Interstitial lung disease at present, or with a history of interstitial pneumonia or Interstitial lung disease requiring hormone treatment in the past, or other Pulmonary fibrosis, organic pneumonia (such as Bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia Subjects with idiopathic pneumonia or evidence of active pneumonia on screening chest computed tomography (CT) images or severely impaired lung function are allowed to have radiation pneumonia in the radiation field; Active tuberculosis. 9. At present, there is active autoimmune disease or a history of autoimmune disease and it may recur (including but not limited to: Autoimmune hepatitis, interstitial pneumonia, Uveitis, enteritis, hypophysitis, Vasculitis, nephritis, hyperthyroidism, hypothyroidism [only subjects that can be controlled through hormone replacement therapy can be included]); Subjects with skin diseases that do not need systematic treatment, such as Vitiligo, psoriasis, alopecia, controlled type I diabetes that receive insulin treatment, or childhood asthma that has completely alleviated without any intervention after adulthood can be included; Asthma subjects requiring medical intervention with Bronchiectasis cannot be included. 10. Suffering from hypertension and unable to achieve good control through antihypertensive medication treatment (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg) (based on the average of BP readings obtained from ≥ 2 measurements), the above parameters are allowed to be achieved through the use of antihypertensive therapy; Previously experienced hypertension crisis or hypertensive encephalopathy. 11. Moderate or severe ascites with clinical symptoms require therapeutic puncture, drainage, or a Child Pugh score>2 (excluding those with only a small amount of ascites displayed on imaging but without clinical symptoms); Uncontrolled or moderate or more Pleural effusion and pericardial effusion. 12. There are clinical cardiac symptoms or diseases that are not well controlled, such as: (1) According to NYHA standards, cardiac dysfunction above Grade II or color Doppler echocardiography: LVEF (left ventricular Ejection fraction)<50%; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within one year before the start of the study treatment; (4) Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; (5) QTc>480ms (QTc interval is calculated using the Fridericia formula; if QTc is abnormal, it can be detected continuously three times every 2 minutes, and the average value is taken). 13. History of spontaneous rupture of liver tumors. 14. People with a history of Hepatic encephalopathy. 15. Previous or current central nervous system metastasis. 16. Subjects with congenital or acquired immune dysfunction (such as those infected with HIV). 17. Thrombosis or embolism events, such as cerebrovascular accident (including Transient ischemic attack, cerebral hemorrhage, cerebral infarction) and Pulmonary embolism, occurred within 6 months before the start of the study treatment. 18. Patients with a history of gastrointestinal bleeding or a clear tendency for gastrointestinal bleeding within 6 months prior to the start of study treatment, such as those at risk of bleeding or severe esophageal and gastric varices, locally active gastrointestinal ulcer lesions, and persistent fecal occult blood positivity, cannot be included in the group. If fecal occult blood positivity is present during the baseline period, a follow-up examination is required. If positive is still present after the follow-up examination, gastroduodenoscopy (EGD) is required, If EGD indicates a risk of bleeding, esophageal and gastric varices/other gastrointestinal diseases cannot be included in the group. 19. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 6 months before the start of the study treatment. 20. There is evidence indicating the presence of intra-abdominal gas accumulation that cannot be explained by puncture or recent surgical procedures. 21. Severe, unhealed or cracked wounds, as well as active ulcers or untreated fractures. 22. Known hereditary or acquired bleeding (such as coagulation dysfunction) or thrombophilia, such as Haemophilia patients; Currently or recently (within 10 days prior to the start of research treatment), full dose oral or injection anticoagulants or thrombolytic drugs (prophylactic use of low-dose aspirin, low-molecular-weight heparin is allowed) have been used for therapeutic purposes. 23. Major Vascular disease (e.g., Aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) occurred within 6 months before the start of study treatment. 24. Has undergone major surgery (excluding diagnosis) within 4 weeks prior to the start of the study treatment or is expected to undergo major surgery during the study period. 25. Have suffered from Bowel obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months before starting the study treatment, including incomplete obstruction related to the original disease or requiring routine parenteral hydration, parenteral nutrition or tube feeding; If the subject with signs/symptoms of incomplete obstruction/obstructive syndrome/Bowel obstruction received definite (surgical) treatment to eliminate symptoms at the time of initial diagnosis, the subject may be admitted to the study. 26. Severe infection within 4 weeks before starting the study treatment, including but not limited to hospitalization due to infection, Bloodstream infections or severe pneumonia complications; Therapeutic antibiotics were administered orally or intravenously within 2 weeks before the start of the study treatment (subjects who received preventive antibiotics, such as preventing urinary tract infection or Chronic obstructive pulmonary disease exacerbation, were eligible to participate in the study). 27. Cannot swallow pills, Malabsorption syndrome or any condition that affects gastrointestinal absorption. 28. It is known that the active ingredients and excipients contained in the research drugs (Camrelizumab, Apatinib, epirubicin) in this study have Hypersensitivity reactions, or have a history of serious allergy to any other monoclonal antibody, anti angiogenesis targeted drugs. 29. Use Immunosuppressive drug or systemic hormone therapy within 14 days before starting the study treatment to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other effective hormones). 30. Strong CYP3A4/CYP2C19 inducers including Rifampicin (and its analogues) and Hypericum perforatum or strong CYP3A4/CYP2C19 inhibitors were used within 14 days before starting the study treatment. 31. They have received live attenuated vaccine treatment within 28 days before starting the study treatment, or are expected to be vaccinated during the treatment of Camrelizumab or within 60 days after the last administration of Camrelizumab. 32. Received other experimental drug treatment within 28 days or 5 half-lives (whichever is longer) before starting the study treatment. 33. According to the judgment of the researchers, the subjects may have other factors that may affect the research results or cause the study to be terminated midway, such as alcohol abuse, drug abuse, other serious illnesses (including mental illness) that require concurrent treatment, serious laboratory test abnormalities, and accompanying family or social factors, which can affect the safety of the subjects.

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Case Record Form, CRF