Phase I/II Study of the Combination of Irinotecan and POF (Paclitaxel Plus Oxaliplatin Plus 5-fluorouracil Plus Leucovorin) and Tislelizumab
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- The maximum dose tolerated
研究概览
简要总结
The purpose of the phase I/II study is to establish the safety of Combination of Irinotecan and paclitaxel with 5-FU, leucovorin, oxaliplatin and Tislelizumab.
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
- •Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.
- •With or without measurable lesions.
- •Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- •Without serious system dysfunction and could tolerate chemotherapy. With normal marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.
- •Life expectancy ≥3 months.
- •With normal electrocardiogram results and no history of congestive heart failure.
- •With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN.
- •Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of Tislelizumab until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug
- •With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
- •With good compliance and agree to accept follow-up of disease progression and adverse events.
排除标准
- •Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
- •Patients with brain or central nervous system metastases, including leptomeningeal disease.
- •Pregnant (positive pregnancy test) or breast feeding.
- •Serious, non-healing wound, ulcer, or bone fracture.
- •Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy.
- •History of a stroke or CVA within 6 months.
- •Clinically significant peripheral vascular disease.
- •Inability to comply with study and/or follow-up procedures.
- •Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.
研究组 & 干预措施
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: Oxaliplatin (Drug)
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: Levo-Leucovorin (Drug)
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: 5-fluorouracil (Drug)
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: Paclitaxel (Drug)
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: Irinotecan (Drug)
POFI and Tislelizumab
This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1.
The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
The maximum dose tolerated
时间窗: 1 month
To determine the maximum tolerated dose of POFI with different doses of irinotecan and paclitaxel combined with Tislelizumab in the first month.
次要结局
- Overall Response Rate(2 years)
- Progression-free survival(2 years)
- Overall survival(2 years)