Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 主要终点
- Disease control rate(DCR)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of Apatinib combined with PD-1 antibody Sintilimab for for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer
详细描述
Patients with advanced gastric cancer (AGC) can be treated with multiple lines of chemotherapy. After second-line treatment some patients may receive third- and subsequent lines of chemotherapy if their performance status is well-preserved and they are willing to receive subsequent active treatments. Apatinib is a small-molecule VEGFR-2 tyrosine kinase inhibitor approved by the CFDA for the treatment of advanced gastric cancer. In a phase III trial, apatinib significantly improved PFS and OS compared with placebo, but the clinical benefit was modest. As a result of toxicity, 850 mg/day Apatinib may cause dose reduction and delay in some patients ,which also caused some doubts. Therefore, it is a reasonable treatment strategy by reducing the dose and combining it with another low-toxic drug to achieve similar or better effects. Some studies have shown that the combination of targeted therapy and immunotherapy may be effective in solid tumor. Sintilimab (IBI308) is a monoclonal antibody targeting programmed death-1 (PD-1). So, the investigators designed an open-label, single-arm, phase II clinical study to evaluate the efficacy and safety of apatinib combined with Sintilimab in Chemotherapy-Refractory Advanced Metastatic Gastric 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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 20-75 years old
- •Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ adenocarcinoma
- •Life expectancy of more than 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1
- •Have failed for at least 2 lines of chemotherapy
- •At least 3 weeks from previous chemotherapy at first dose of trial drug
- •Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTC) (except for the laboratory values)
- •Failure of prior palliative chemotherapy/chemotherapies (at least one irinotecan- or cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment.
- •At least one measurable lesion defined by RECIST 1.1 as determined by investigator assessment.
- •Has adequate organ function
- •At least 4 weeks from any major surgery (at first dose of trial drug)
- •Patients must be able to swallow apatinib
排除标准
- •In the past, participants have received anti PD-1, anti PD-L1 or anti PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (such as Cytotoxic T-Lymphocyte Antigen 4 [CTLA-4] and CD137)
- •Other co-existing malignancies or malignancies diagnosed within the last 5 years(except cured cutaneum carcinoma or carcinoma in situs of cervix)
- •Less than 4 weeks from the last clinical trial
- •Active and uncontrollable bleeding from gastrointestinal tract
- •Known history of QT interval prolongation, ongoing QT prolongation (> 450 msec for males or > 470 msec for females), any cardiac ventricular dysrhythmias, atrial fibrillation of any grade
- •Hypertension that cannot be controlled by medications (> 140/90 mmHg despite optimal medical therapy)
- •Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed;
- •Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
- •Active uncontrolled infection
- •Known human immunodeficiency virus (HIV) infection
- •Symptomatic central nervous metastasis and/or cancerous meningitis
- •Known allergic/hypersensitivity reaction to any of the components of the treatment; or known drug abuse/alcohol abuse
- •Pregnant or lactating women
研究组 & 干预措施
Apatinib+Sintilimab
Apatinib 500mg qd p.o and Sintilimab 200mg intravenously on day 1 every 3 weeks until disease progression or intolerable toxicity or patients withdrawal of consent
干预措施: Apatinib Mesylate (Drug)
Apatinib+Sintilimab
Apatinib 500mg qd p.o and Sintilimab 200mg intravenously on day 1 every 3 weeks until disease progression or intolerable toxicity or patients withdrawal of consent
干预措施: Sintilimab (Drug)
结局指标
主要结局
Disease control rate(DCR)
时间窗: 12 months
The percentage of patients who have achieved complete response, partial response and stable disease,evaluated by RECIST, confirmed at least 4 weeks following the date of the initial response.
次要结局
- Objective Response Rate (ORR)(12 months)
- Overall survival (OS)(up to 12 months)
- Duration of Response (DOR)(up to 12 months)
- Progression Free Survival (PFS)(up to 12 months)
- Adverse events（AE）(up to 12 months)