A Single-arm Phase II Clinical Study Evaluating the Efficacy and Safety of Systemic Chemotherapy(mFOLFOX7) Combined With Camrelizumab and Apatinib in BCLC Stage A/B Hepatocellular Carcinoma Patients Beyond Milan Criteria
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Major pathological response (MPR) rate
研究概览
简要总结
This study was designed to evaluate the effectiveness and safety of mFOLFOX7（Oxaliplatin,Calcium Levofolinate,Fluorouracil） combined with Apatinib and Camrelizumab for Hepatocellular Carcinoma.
The primary outcome measure is to evaluate the primary pathological response (MPR) rate of the therapy for Hepatocellular Carcinoma.
The secondary Outcome measures include the objective response rate (ORR), the duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) [ Time Frame: 6- and 12-month], overall survival rate (OSR) [ Time Frame: 6- and 12-month], the median progression-free survival time (mPFS) and median overall survival time (mOS) of the therapy for Hepatocellular Carcinoma.
Moreover, this study aims to assess the safety and tolerability of the Therapy for Hepatocellular Carcinoma.
详细描述
Hepatocellular carcinoma(HCC) is a common high-grade malignant tumor in my country, with limited treatment options and poor prognosis.
Early and middle stage (BCLC A or B) surgical resection is the main curative method for liver cancer, except for a few very early stages. Small liver cancer has a high short-term recurrence rate after surgery, with a median survival time of about 2 years and a 5-year survival rate of<20%. Treatment objectives for advanced liver cancer.
Previously, systemic therapy and transcatheter arterial chemoembolization(TACE) were mainly used for treatment, while targeted therapy and immunotherapy in systemic therapy have made rapid progress in recent years.
Trastuzumab and chemotherapy can increase the ORR of human epidermal growth factor receptor 2(HER2) positive advanced gastric cancer from 51.9% to 74.4%.
Preliminary small sample studies have shown that veins the combination of mFOLFOX7 regimen with Carolizumab and Apatinib may be a potential treatment for CNLC stage III hepatocellular carcinoma.A strategy that is effective, safe, and easy to implement, with preliminary research results similar to FOLFOX-HAIC combined with targeted immunotherapy. Especially for patients with concomitant main portal vein tumor thrombus showed very good results, and the extremely low microvascular invasion(MVI) in postoperative pathology also suggests the possibility of good therapeutic value for microvascular metastasis of liver cancer.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Before treatment, histologically or cytologically or clinically diagnosed as hepatocellular carcinoma (HCC) and the clinical stage belongs to BCLC stage A/B HCC that exceeds the Milan criteria.
- •Child-pugh liver function grading: Grade A or B
- •Did not received any type of other first-line drugs such as Sorafenib or Lenvatinib.
- •According to RECIST 1.1 standard and mRECIST standard, patients have at least one measurable lesion (CT scan long diameter ≥10mm and the lesion has not received radiotherapy, freezing or other local treatments)；
- •ECOG PS score 0-2;
- •Expected survival ≥ 12 weeks;
- •Blood routine:White blood cells count ≥3.0×10^9/L Platelet count ≥70×10^9/L Hemoglobin ≥80g/L(without blood transfusion within 14 days); kidney function: Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN); Liver function:Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); AST or ALT levels ≤ 3 times the upper limit of normal value (ULN)
- •Patients with hepatitis B or C coinfection need to use antiviral drugs and have not used interferon.
- •Women of childbearing age should have a negative serum or urine pregnancy test within 7 days before enrollment and they must be non-lactating patients and agree to use contraceptive measures during the study period and within 6 months after the end of the study. Men should agree to use contraceptive measures during the study period and within 6 months after the end of the study period.
- •Patients volunteered to participate in this study and signed informed consent;
排除标准
- •Have received immunotherapeutic drugs or interferon in the past.
- •Allergic to the drugs in the treatment ;
- •Female subjects with pregnancy or on feeding.
- •Have received other immunotherapy drugs (targeting PD1/PDL1).
- •Patients with combined uncontrolled cardiac clinical symptoms or diseases, such as: (1) heart failure above NYHA class II; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; (5) those with poorly controlled hypertension by drugs and assessed by doctors as having a high risk of using apatinib.
- •Past medical history includes other tumors or a second tumor, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ and papillary thyroid cancer.
- •Combined with severe infection (CTCAE greater than grade 2) before the start of treatment, such as severe pneumonia requiring hospitalization, active tuberculosis, bacteremia, infectious complications, etc.; baseline chest imaging examination indicates active pulmonary inflammation. There are symptoms and signs of infection within 2 weeks before the first use of the study drug or oral or intravenous antibiotic treatment is required (excluding prophylactic use of antibiotics).
- •Have a history of immunodeficiency, such as positive HIV monitoring, have other acquired or congenital immunodeficiency diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes), or have a history of organ transplantation or bone marrow transplantation; or are taking hormones or other immunosuppressive drugs orally or intravenously; but excluding vitiligo or cured childhood asthma/allergies, and patients who do not require any intervention as adults.
- •Severe coagulation disorders (INR>2.0, PT>16s), those with obvious bleeding tendencies (including but not limited to vomiting blood and having bloody stools every day in the past 3 months).
- •Have the history of abusing psychotropic drugs and unable to quit ,or with mental disorders; with brain metastases or hepatic encephalopathy.
- •As judged by the investigator, the patient may have other factors that may cause the study to be terminated prematurely, such as other serious diseases or serious abnormal laboratory tests or accompanied by other family or social factors that will affect the safety of the subject or the collection of trial data and samples.
研究组 & 干预措施
mFOLFOX7 combined with Apatinib and Camrelizumab
mFOLFOX7(Oxaliplatin, Calcium Levofolinate, Fluorouracil) combined with Apatinib and Camrelizumab
干预措施: mFOLFOX7 combined with Camrelizumab and apatinib (Drug)
结局指标
主要结局
Major pathological response (MPR) rate
时间窗: 6 months
MPR rate is defined as the proportion of participants with =\<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.
次要结局
- Objective Response Rate(ORR) by RECIST 1.1(6 months)
- pathologic complete response (pCR) rate(6 months)
- Duration of remission(DOR) by mRECIST(12 months)
- Disease Control Rate(DCR) by mRECIST(6 months)
- Disease-free-survival(DFS) by RECIST 1.1(12 months)
- Progression-Free Survival (PFS) by RECIST 1.1(12 months)
- Overall Survival (OS) by RECIST 1.1(24 months)
- Progression-Free Survival rate (PFSR) by RECIST 1.1(12 months)
- Overall Survival Rate (OSR) by RECIST 1.1(24 months)