NCT04443309招募中1 期
A Single-arm, Non-randomized, Single-center Study to Evaluate Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a single arm, open-label, non-randomized and single-center phase I/II clinical study, to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as first-line therapy in patients with advanced Hepatocellular Carcinoma.
详细描述
The purpose of this study is to evaluate the safety, tolerance and efficacy of Lenvatinib combined with Camrelizumab as first-line therapy for patients with advanced hepatocellular carcinoma.The target sample size is 53.In the first phase 6 panticipants was evaluated (N=3+3), If there was no obvious dose-limiting toxicity (DLT), then entered the extended phase (N=47).Treatment continually until disease progression or intolerable toxicity or patients withdrawal of consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol;
- •Males or females, age ≥ 18 years at the time of informed consent;
- •Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer 2017 in China) or histopathologically or cytologically confirmed advanced HCC;
- •BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy;
- •No previous systematic treatment for HCC;
- •Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan;
- •ECOG-PS score 0 or 1
- •Child-Pugh Class: Grade A
- •Life Expectancy of at least 3 months
- •Subjects with HBV infection: HBV DNA<2000 IU/ml or <10^4 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with HCV-RNA(+) must receive antiviral therapy;
- •Hematology and organ functions are sufficient based on the following laboratory results within 14 days prior to the treatment of this study:
- •Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no drugs use): WBC ≥ 3.0×10^9/L, HB ≥ 85 g/L; Neutrophils ≥ 1.5×10^9/L; PLT≥75×10^9/L; Biochemical examination (no ALB infused within 14 days): ALB ≥ 29 g/L; ALP and ALT and AST < 5×ULN; TBIL≤3×ULN; Adequate renal function: Cr≤1.5×ULN, or CCr>50mL/min; Female: CrCl = ((140- year) x weight (kg) x 0.85)/72x Cr (mg/dL) Male: CrCl = ((140- year) x weight (kg) x 1.00)/72xCr (mg/dL)
- •Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive methods with an annual contraceptive failure rate of less than 1% during treatment and for at least 6 months after the last administration.
排除标准
- •Hepatocellular carcinoma patients with any of the following:
- •Suitable for radical surgery; without an assessment lesion after radical surgery; liver transplantation history or ready for liver transplantation;
- •History of hepatic encephalopathy;
- •Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma;
- •Pregnant women (positive pregnancy test before taking medicine) or lactating women;
- •Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug (or any excipient);
- •Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection;
- •Previous or existing CTCAE 5.0 standard grade 3 or above gastrointestinal fistula or non-gastrointestinal fistula (such as skin);
- •Factors to affect oral administration and absorption (such as inability to swallow, chronic diarrhea and intestinal obstruction);
- •Ascites with clinical symptoms (i.e. ascites with Child-Pugh rating > 2) or cancerous ascites require therapeutic abdominal puncture or drainage. Or uncontrolled malignant ascites (ascites that researchers believe diuretics or puncture cannot control);
- •Major surgical operations (except biopsy) were performed within 4 weeks prior to the first study of drug therapy or the surgical incision was not completely healed; Minor surgery (i.e. simple resection, biopsy, etc.) was performed within 7 days before the first round of research intervention.
- •Cardiovascular and cerebrovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accident or transient ischemic attack, congestive heart failure occurred within 6 months prior to admission (New York Heart Association Grade ≥2, see Appendix 4); Arrhythmia requiring antiarrhythmic drugs (except β receptor blocker or digoxin); Repeated ECG detection QTcF interval>480 milliseconds (ms).
- •Hepatic and renal insufficiency, such as jaundice, ascites, and/or bilirubin>3×ULN, creatinine ratio>3.5g/24h, or renal failure requiring blood or peritoneal dialysis, etc. And/or urine routine showed proteinuria ≥++or confirmed 24-hour proteinuria>1.0g.
- •Persistent>2 grade (CTC-AE5.0) infection.
- •History of thromboembolism (including stroke and/or transient ischemic attack) in the past 6 months.
- •Hypertension (systolic blood pressure>160mmHg, diastolic blood pressure>100 mmHg) that not be well controlled through antihypertensive drug treatment.
- •History of active autoimmune diseases or autoimmune diseases in the past two years.
- •Known central nervous system metastasis and/or cancerous meningitis.
- •Be ready for or previously received organ or allogenic bone marrow transplantation.
- •Known history of active tuberculosis (Mycobacterium tuberculosis).
- •History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage.
- •History of human immunodeficiency virus (HIV)infection.
- •Active hepatitis B virus or C virus infection and not receive regular treatment;
- •Serious non-healing wound, ulcer or fracture.
- •Drug abuse exists; or any medical, psychological or social condition that may affect research, unstable patient compliance or even endanger patient safety.
- •Any>1 grade (CTC-AE 5.0) unresolved toxicity due to previous treatment or operation, except for hair loss, anemia, and hypothyroidism.
- •Previous and current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and severe impairment of lung function.
- •Received a potent CYP3A4 inhibitor treatment within 7 days prior to the study or received a potent CYP3A4 inducer within 12 days prior to the study.
- •With other active malignant tumors except HCC within 5 years or simultaneously.
- •Patients are unsuitable for participation in this research after comprehensive assessment by the researchers.
- •Patients participate in another clinical study at the same time.
研究组 & 干预措施
Lenvatinib plus Camrelizumab
Experimental
Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.
Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
干预措施: Camrelizumab (Drug)
Lenvatinib plus Camrelizumab
Experimental
Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.
Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: one year
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
次要结局
- Overall Survival (OS)(one year)
- 3-months and 6-months Progression Free Survival Rate(6 months)
- Progression-free Survival (PFS)(one year)
- Duration of Response (DOR)(one year)
- Clinical Benefit Rate (CBR)(two years)
- 6-months and 1-year Mortality Rate(one year)
- Disease Control Rate (DCR)(one year)
- Adverse Events (AE)(two years)
研究者
研究点 (1)
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