Explorative Trial to Investigate Catumaxomab (Anti-EpCAM x Anti-CD3) for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas Prior to Gastrectomy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Rate of macroscopic complete remissions of peritoneal carcinomatosis
研究概览
简要总结
The purpose of this study is to determine the efficacy of catumaxomab by determination of the rate of macroscopic complete remissions of peritoneal carcinomatosis after treatment with one cycle (four doses) of catumaxomab followed by six cycles of routine neoadjuvant chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of resectable gastric adenocarcinoma or adenocarcinoma of the esophagogastric junction (type II and type III according to Siewerts classification)
- •Macroscopic peritoneal carcinomatosis (stage P1-4 according to Gilly et al., appendix 1)
- •Patients potentially eligible for gastrectomy after primary systemic (and intraperitoneal) treatment
- •Signed and dated informed consent before the start of specific protocol procedures
- •Age > 18 years
- •ECOG Performance Status of 0 or 1
- •Life expectancy of at least 12 weeks
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
- •Hemoglobin > 10.0 g/dl
- •Leukocyte count > 4.000/μl; absolute neutrophil count (ANC) > 2.000/μl
- •Platelet count > = 100.000/µl
- •Total bilirubin < 1,5 times the upper limit of normal
- •ALT and AST < 3 x upper limit of normal
- •Alkaline phosphatase < 5 x ULN
- •Serum creatinine < 1.5 x upper limit of normal and creatinine clearance > 60 ml/min
- •The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations
排除标准
- •Distant metastasis other than peritoneal seedings
- •Prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry
- •Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = < 1 year before enrolment
- •History of HIV infection or chronic hepatitis B or C
- •Active, clinically serious infections (> grade 2 NCI-CTC version 3.0)
- •Pre-existing neuropathy > grade 1 (NCI CTCAE), except for loss of tendon reflex
- •Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
- •History of organ allograft
- •Patients undergoing renal dialysis
- •Known hypersensitivity to any of the drugs given in the study; known hypersensitivity to murine (rat and/or mouse) proteins
- •Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- •Excluded therapies and medications, previous and concomitant:
- •Prior anti-cancer chemotherapy or immunotherapy.
- •Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- •Major surgery within 4 weeks of starting the study, and patients must have recovered from effects of major surgery
- •Pregnant or breast-feeding patients, or planning to become pregnant within 6 months after the end of treatment. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and for 6 months after the end of treatment
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's understanding of the informed consent procedure, participation in the study or evaluation of the study results
研究组 & 干预措施
catumaxomab
this arm was stopped. the antibody previously used as a study drug is not available at this time. patients will be randomized only into the standard arm
[Catumaxomab: 4 intraperitoneal infusions of catumaxomab at an escalating dose of 10µg (d0), 20µg (d3), 50µg (d7), and 150µg (d10) and 7 days after the last catumaxomab infusion FLOT; 6 cycles q2w: Fluorouracil 2600 mg/m² as 24h infusion (d1) , leucovorin 200mg/m² (d1), oxaliplatin 85 mg{m² (d1), docetaxel 50 mg/m² (d1))
干预措施: catumaxomab, Fluorouracil, leucovorin, oxaliplatin, docetaxel (Drug)
standard therapy
FLOT; 6 cycles q2w:
Fluorouracil 2600 mg/m² as 24h infusion (d1) leucovorin 200mg/m² (d1) oxaliplatin 85 mg{m² (d1) docetaxel 50 mg/m² (d1)
干预措施: Fluorouracil, leucovorin, oxaliplatin, docetaxel (Drug)
结局指标
主要结局
Rate of macroscopic complete remissions of peritoneal carcinomatosis
时间窗: Assessment after 14 - 18 weeks after start of treatment
Macroscopic complete response (mCR) rate of the peritoneal lesions, as resulting from the second diagnostic laparoscopy or laparotomy performed after chemotherapy.
次要结局
- Overall survival (OS)(Assessment over minimum 16 months up to 3 years)
- Immunoreaction against tumor in tissue samples(14 - 18 weeks)
- Frequency, relationship, and severity of AEs(Assessment over minimum 16 months up to 3 years)
- Detection of disseminated tumor cells via PCR(14 - 18 weeks)
- Surgical resection rate (R0, R1, R2)(Assessment after 14 - 18 weeks after start of treatment)
- Disease-free survival (DFS)(Assessment over minimum 16 months up to 3 years)
- Progression-free survival (PFS)(Assessment over minimum 16 months up to 3 years)