Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 主要终点
- Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
研究概览
简要总结
The interest in using L-asparaginase in pancreatic cancer arose from in vitro and in vivo studies data showing an anti-neoplastic effect on pancreatic tumor cell lines. Interestingly, these studies suggest an additional effect of L-asparaginase associated to gemcitabine.GRASPA is a suspension of red blood cells encapsulating L-asparaginase. The aim of this phase I clinical trial is to evaluate the Maximum Tolerated Dose (MTD) of GRASPA on locally advanced or metastatic pancreatic tumors, after therapy failure of first or second line chemotherapy using gemcitabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Exocrine pancreatic adenocarcinoma cytologically or histologically confirmed
- •Locally advanced and non-resectable with invasion of the superior mesenteric artery (stage III) or metastatic (stage IV) as defined by TNM (primary tumor, regional nodes, metastasis) 2002 classification (UICC 2002)
- •resistant to a first or second line chemotherapy with gemcitabine
- •Patient aged between 18 to 70 years
- •Signed Informed Consent Form
- •Life expectancy ≥ 12 weeks
- •Accurate measurement of tumor volume by imagery (in at least one dimension)
- •Presence of one or several tumor markers (carcinoembryonic antigen [CEA] and cancer antigen [CA] 19.9)
- •Eastern Cooperative Oncology Group [ECOG] Prognostic Score : 0, 1 or 2
- •Patient beneficiary of a Social Security Insurance
排除标准
- •Patient with an endocrine or acinar pancreatic tumor
- •Patient with known or suspected cerebro-meningeal metastases
- •Haemoglobin level greater than 13 g/L
- •Patient hypersensitive to L-asparaginase or have had prior exposure to any form of L-asparaginase
- •Splenic vein thrombosis < 3 months or under active treatment
- •Anti-vitamin K treatment
- •Hepatic Insufficiency unrelated to pancreatic cancer
- •Renal insufficiency unrelated to pancreatic cancer
- •Pancreatitis or pancreatitis history unrelated to pancreatic cancer
- •Insulin-dependant diabetes mellitus unrelated to pancreatic cancer
- •Current or prior coagulopathy disorders unrelated to pancreatic cancer
- •ECOG Prognostic Score 3 or 4
- •History of grade 3 blood transfusion reaction (life threatening situation)
- •Presence of rare and dangerous anti-erythrocyte antibodies preventing from getting a compatible packed Red Blood Cells for the patient
- •Patient already included in another clinical trial
- •Pregnancy, breast-feeding or absence of secured contraception
- •Unwillingness to sign the informed consent form
研究组 & 干预措施
GRASPA 25
干预措施: GRASPA (Drug)
GRASPA 50
干预措施: GRASPA (Drug)
GRASPA 100
干预措施: GRASPA (Drug)
GRASPA 150
干预措施: GRASPA (Drug)
结局指标
主要结局
Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
时间窗: 4 weeks
Dose limiting toxicities were defined according to CTCAE v3.0 as follow: Known toxicities related to asparaginase: * Pancreatic grade 2, 3 or 4 * Allergic, Neurological, Hepatic, Coagulation grade 3 or 4 an any other toxicity of grade 4
次要结局
- Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)(8 weeks)
- Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax(Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56)
- Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life(Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56)
- Number of Patient Positive for Anti-L-asparaginase Antibodies(Day 0, 1, 28 and 56)
- Summary of CA 19.9 Over Time(Day 0, 28 and 56)
- Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity(Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56)
- Change of Asparagine Levels From Baseline (Pharmacodynamics)(Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56)
- Summary of CEA Level Over Time(Day 0, 28, 56)