|
研究疾病：
|
肝癌
|
研究疾病代码：
|
|
|
Target disease：
|
primary liver cancer
|
Target disease code：
|
|
研究类型：
Study type：
|
治疗研究
Treatment study
|
研究设计：
Study design：
|
单臂
Single arm
|
|
研究所处阶段：
Study phase：
|
II期临床试验
Phase II clinical trial
|
|
研究目的：
|
观察和评价复方黄黛片治疗晚期原发性肝癌的临床疗效和安全性
|
|
Objectives of Study：
|
To observe and evaluate the clinical efficacy and safety of compound Huangdai tablet in the treatment of advanced primary liver cancer
|
|
药物成份或治疗方案详述：
|
基础治疗+复方黄黛片
基础治疗：最佳支持治疗，具体治疗方案参照《原发性肝癌诊疗规范（2019年版）》确定，可根据实际情况调整（详细记录剂量调整及药物加减）
复方黄黛片用法用量：口服，5~10片/次，3次/日，每3个月为一个循环周期，间歇14d
|
|
Description for medicine or protocol of treatment in detail：
|
Basic treatment + compound Huangdai tablets
Basic treatment: the best supportive treatment. The specific treatment scheme is determined according to the standard for diagnosis and treatment of primary liver cancer (2019 Edition), which can be adjusted according to the actual situation (record the dose adjustment and drug addition and subtraction in detail)
Usage and dosage of compound Huangdai tablets: oral, 5 ~ 10 tablets / time, 3 times / day, every 3 months as a cycle, with an interval of 14 days
|
|
纳入标准：
|
1.年龄在18-75岁（含），性别不限；
2.符合2019年版《原发性肝癌诊疗规范》临床诊断标准或经病理组织学或细胞学确诊肝细胞肝癌；
3.不能接受或不愿接受姑息性手术治疗的，且有至少一个可测量的病灶（根据RECIST 1.1版要求该可测量病灶螺旋CT扫描长径≥10mm或肿大淋巴结短径≥15mm）
4.既往接受过全身性化疗（以奥沙利铂为基础的化疗）或靶向治疗（如索拉非尼、仑伐替尼等）有耐药性或不耐受。耐药性被定义为在治疗期间或治疗后的疾病进展或复发，且接受化疗至少持续一个周期，接受靶向治疗至少持续14天。不耐受被定义为4级或更高的血液毒性、3级或以上的非血液毒性，或2级或更高的毒性。
5.Child-Pugh：A-B级、BCLC分期：B-C期；
6.ECOG PS评分：0-3分；
7.肝肾器官功能正常，即符合下列标准：
a)血常规检查：①HB≥90 g/L；②ANC≥1.5×109/L；③PLT≥75×109/L；
b)生化检查：①ALB ≥29 g/L；②ALT和AST＜5ULN；③TBIL≤2ULN；④肌酐≤1.5ULN。
8.预计生存期≥12周；
9.不愿或不能接受二线靶向和（或）免疫治疗者
自愿参加本项临床试验，签署知情同意书，并能完成随访
|
|
Inclusion criteria
|
1. 18-75 years old (inclusive), regardless of gender;
2. Meet the clinical diagnostic criteria of the standard for diagnosis and treatment of primary liver cancer (2019 Edition) or the diagnosis of hepatocellular carcinoma by histopathology or cytology;
3. Those who cannot accept or are unwilling to accept palliative surgery and have at least one measurable lesion (according to RECIST version 1.1, the long diameter of spiral CT scanning of the measurable lesion is ≥ 10mm or the short diameter of enlarged lymph nodes is ≥ 15mm)
4. Previous systemic chemotherapy (oxaliplatin based chemotherapy) or targeted therapy (such as sorafenib, renvatinib, etc.) with drug resistance or intolerance. Drug resistance is defined as disease progression or recurrence during or after treatment, and receiving chemotherapy for at least one cycle and targeted therapy for at least 14 days. Intolerance is defined as grade 4 or higher hematotoxicity, grade 3 or higher non hematotoxicity, or grade 2 or higher toxicity.
5. Child Pugh: grade A-B, BCLC stage: stage B-C;
6. ECoG PS score: 0-3;
7. If the liver and kidney organs function normally, they meet the following standards:
a) Blood routine examination: ① HB ≥ 90 g / L; ②ANC≥1.5 × 109/L ③PLT≥75 × 109/L
b) Biochemical examination: ① ALB ≥ 29 g / L; ② ALT and AST < 5uln; ③TBIL≤2ULN； ④ Creatinine ≤ 1.5uln.
8. Estimated survival time ≥ 12 weeks;
9. Unwilling or unable to accept second-line targeted and / or immunotherapy
Voluntarily participate in the clinical trial, sign the informed consent form, and be able to complete the follow-up
|
|
排除标准：
|
1.已知对研究药物或有效成分过敏的患者；
2.肝癌的影像学表现与以下任何一项相对应：a）≥50%肝占位的HCC；b）明确侵入胆管；c）门静脉侵犯主门静脉分支（VP4）；
3.混合细胞癌及纤维板层细胞癌；以往（5年内）或同时患有其它未治愈的恶性肿瘤，对于已治愈的皮肤基底细胞癌和宫颈原位癌除外；
4.入组前4周内接受过以下治疗：手术、放疗、化疗、局部治疗（肝动脉栓塞化疗、肝动脉灌注化疗、射频消融、冷冻消融或经皮无水乙醇注射）、靶向治疗及生物治疗者；
5.有临床症状的腹水，即需要治疗性腹腔穿刺或引流；
6.患有高血压且经降压药物治疗无法降至正常范围内者（收缩压＞140 mmHg，舒张压＞90 mmHg）；
7.患有Ⅱ级以上心肌缺血或心肌梗塞、控制不良的心律失常（包括QTc间期男性≥450 ms、女性≥470 ms）；
8.凝血功能异常（INR＞1.5或凝血酶原时间（PT）＞ULN+4秒），具有出血倾向或正在接受溶栓或抗凝治疗；
9.按照NYHA标准Ⅲ～Ⅳ级心功能不全或心脏彩超检查：LVEF（左室射血分数）＜50%；
10.入组前3个月内有消化道出血病史或具有明确的胃肠道出血倾向，如：有出血危险的食道静脉曲张、局部活动性溃疡病灶、大便潜血≥（++）不可入组；如大便潜血（+），要求进行胃镜检查；
11.受试者存在免疫缺陷性疾病或病史，或有器官移植史，或准备进行肝移植的患者；
12.具有影响口服药物的多种因素（如无法吞咽、慢性腹泻和肠梗阻，明显影响药物服用和吸收的情况）；
13.已经发生中枢神经系统转移或已知的脑转移患者；
14.任何受试者因对CT和MRI对比剂过敏或其他禁忌症而不能通过三相肝CT或三相肝MRI进行评估；
15.有精神疾病，或者精神类药物滥用史；
16.正在参加其它临床研究或在入组前30天内正在接受任何其他研究治疗的患者；
17.妊娠期或哺乳期妇女；有生育能力的患者不愿或无法采取有效的避孕措施；
经研究者判断，不适宜纳入本研究的患者。
|
|
Exclusion criteria：
|
1. Patients known to be allergic to the study drug or active ingredient;
2. The imaging findings of liver cancer correspond to any of the following: a) ≥ 50% HCC; b) Clear invasion of bile duct; c) Portal vein invaded the main portal vein branch (VP4);
3. Mixed cell carcinoma and fibrous lamellar cell carcinoma; Other untreated malignant tumors in the past (within 5 years) or at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ;
4. Those who have received the following treatment within 4 weeks before enrollment: surgery, radiotherapy, chemotherapy, local treatment (hepatic artery chemoembolization, hepatic artery infusion chemotherapy, radiofrequency ablation, cryoablation or percutaneous absolute ethanol injection), targeted therapy and biotherapy;
5. Ascites with clinical symptoms, i.e. therapeutic abdominal puncture or drainage;
6. Patients with hypertension who cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
7. Arrhythmias with myocardial ischemia or myocardial infarction above grade II and poor control (including QTc interval ≥ 450 ms for men and ≥ 470 MS for women);
8. Abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
9. According to NYHA standard, grade III ~ IV cardiac insufficiency or color Doppler echocardiography: LVEF (left ventricular ejection fraction) ＜ 50%;
10. Patients who have a history of gastrointestinal hemorrhage or have a clear tendency of gastrointestinal bleeding within 3 months before enrollment, such as esophageal varices with bleeding risk, local active ulcer lesions and fecal occult blood ≥ (+) shall not be enrolled; If stool occult blood (+), gastroscopy is required;
11. The subject has immune deficiency disease or history, or has a history of organ transplantation, or is ready for liver transplantation;
12. There are many factors affecting oral drugs (such as inability to swallow, chronic diarrhea and intestinal obstruction, which significantly affect the taking and absorption of drugs);
13. Patients with central nervous system metastasis or known brain metastasis;
14. Any subject cannot be evaluated by three-phase liver CT or three-phase liver MRI due to allergy to CT and MRI contrast agents or other contraindications;
15. Have a history of mental illness or psychotropic substance abuse;
16. Patients who are participating in other clinical studies or receiving any other research treatment within 30 days before enrollment;
17. Pregnant or lactating women; Patients with fertility are unwilling or unable to take effective contraceptive measures;
In the judgment of the investigator, the patients are not suitable for inclusion in this study.
|
|
研究实施时间：
Study execute time：
|
从From
2021-09-15
至To
2023-03-15
|
征募观察对象时间：
Recruiting time：
|
从From
2021-10-08
至To
2022-10-08
|
