Efficacy and Safety of Intraperitoneal Immune Checkpoint Inhibitors and Zoledronic Acids in Gastric Cancer Malignant Ascites: a Phase I/II Clinical Study (IPIZA)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT) or maximal tolerance dose (MTD) in the Phase Ib stage
研究概览
简要总结
This study is to evaluate the safety and efficacy of intraperitoneal injection of immune checkpoint inhibitor combined with zoledronic acid for the treatment of malignant ascites in gastric cancer.
This study is a phase Ib/II clinical study to evaluate the safety and efficacy of intraperitoneal injection of immune checkpoint inhibitors in combination with zoledronic acid in the treatment of malignant ascites in gastric cancer, which consists of two phases, firstly, the phase Ib safety study, which adopts the '3+3' drug-escalation experimental design, and after determining the safe and tolerable dose, it will proceed to the second part of the phase II efficacy study. The Phase II study was designed by Simon's two-stage approach to evaluate the efficacy of immune checkpoint inhibitors in combination with zoledronic acid in the treatment of malignant ascites in 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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gastric adenocarcinoma diagnosed pathologically;
- •Malignant ascites confirmed by ascites cytology;
- •Presence of ascites confirmed by CT with ascites graded as 2nd and 3rd degree (EASL guidelines and ICA consensus);
- •Those aged 18-75 years;
- •Patients who had not undergone local administration of drugs in the abdominal cavity and systemic immunotherapy within the previous 4 weeks;
- •Vital signs are stable, Karnofsky score (≥70), and expected survival time is >3 months;
- •Normal bone marrow haematopoietic function, blood routine: HGB ≥90g/L, WBC ≥2.5×10^9/L (NEU ≥1.5×10^9/L), PLT ≥90×10^9/L;
- •Normal coagulation function without bleeding tendency (International normalised ratio of prothrombinogen INR<1.5);
- •Liver function: total bilirubin ≤1.5 times the upper limit of normal (ULN); AST and ALT ≤2 times the upper limit of normal (ULN) (or ≤5 times the upper limit of normal (ULN) if the abnormalities are mainly due to tumour infiltration);
- •Renal function: Cr ≤1.5 times the upper limit of normal (ULN) or creatinine clearance ≥60mL/min.
排除标准
- •Non-malignant ascites (e.g., portal hypertension ascites or infected ascites);
- •Presence of contraindications to immunotherapy (including long-term hormone use, history of radiation pneumonitis, radiation hepatitis, radiation enteritis, etc.);
- •Combination of other serious cardiopulmonary diseases that affect the treatment, etc;
- •Patients with extensive abdominal adhesions; encapsulated peritoneal fluid; history of intestinal obstruction; and malignant patients with extensive distant metastases in the terminal stage;
- •Women who are breastfeeding, pregnant, or preparing for pregnancy;
- •Patients with plasma albumin (ALB) <30 g/L and severe hypoproteinemia;
- •Patients with known hypersensitivity to components of the test drug or its analogues;
- •Patients with other severe, acute or chronic diseases that may interfere with the interpretation of the study results and who, in the judgement of the investigator, are unsuitable for participation in the clinical trial;
- •Patients with cognitive dysfunction, or poor treatment compliance as judged by the investigator;
- •Participants in other clinical trials within 4 weeks;
- •Combination of other malignancies;
- •Those who, in the opinion of the investigator, are not suitable for participation in the clinical trial.
研究组 & 干预措施
zoledronic acid plus Sintilimab intraperitoneal injection therapy arm
patients will receive zoledronic acid 0.5-1mg plus Sintilimab 1.0mg/kg intraperitoneal injection
干预措施: zoledronic acid plus Sintilimab intraperitoneal injection (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT) or maximal tolerance dose (MTD) in the Phase Ib stage
时间窗: 28 days after the last treatment
Side effects of drug or treatment that are serious enough (e. g. ≥Grade 3 non-hematologic toxicity according to CTCAE 5.0 in ≥1/3) to prevent an increase in dose or level of that treatment. The MTD is defined as the previous dose level.
Objective response rate
时间窗: 4 weeks after last treatment
Complete remission (CR): complete resolution of ascites and maintained for more than 4 weeks; complete disappearance of all target lesions; Partial remission (PR): the amount of CT-measured ascites decreased by more than 50% compared to pretreatment and the amount of ascites withdrawn again was less than 1/2 of the previous withdrawal and was maintained for more than 4 weeks; the sum of the diameters of all measurable target lesions was ≥30% below baseline; Objective Response Rate（ORR） = CR + PR
次要结局
- Immune cell changes(4 weeks)
- Rates of Adverse events according to CTCAE 5.0 in overall subjects(3 months after the last treatment)
- Time for ascites control(1 year)
- Quality of Life Assessment(1 year)
研究者
Lian Liu, MD, PHD
Professor
Qilu Hospital of Shandong University