Concomitant Intraperitoneal and Systemic Chemotherapy in Patients with Extensive Peritoneal Carcinomatosis of Gastric Origin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Maximum-tolerated dose
研究概览
简要总结
Gastric cancer with peritoneal carcinomatosis has a poor prognosis, with little treatment options available. The current treatment strategy consists of palliative systemic chemotherapy. However, previous research suggests that systemic chemotherapy is less effective against peritoneal carcinomatosis than against metastases that spread hematogenously.
Several studies suggested that in patients with peritoneal carcinomatosis, intraperitoneal chemotherapy (IP) may be superior compared to intravenous chemotherapy. Intraperitoneal chemotherapy could lead to higher concentrations of chemotherapy in the peritoneal cavity for a longer period of time, resulting in an increased cumulative exposure to the peritoneal metastases. A few Asian studies have shown promising results with intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of gastric origin. However, intraperitoneal chemotherapy combined with systemic chemotherapy has not been investigated in Western patients with peritoneal carcinomatosis of gastric origin yet. The objective of this trial is to establish the maximum tolerated dose (MTD) of intraperitoneal administration of irinotecan, added to systemic capecitabine/oxaliplatin (CAPOX) in patients with peritoneal carcinomatosis of gastric origin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients with a histologically confirmed diagnosis of HER2-negative gastric cancer.
- •A histologically confirmed diagnosis of peritoneal carcinomatosis.
- •Age ≥ 18 years old.
- •Written informed consent according to the ICH-GCP and national/local regulations.
- •A peritoneal cancer index (PCI) ≥7 evaluated by laparoscopy or laparotomy before inclusion in this trial.
- •Patients must be ambulatory: World Health Organisation (WHO) performance status 0 or
- •Life expectancy of at least 3 months.
- •Ability to return to the Erasmus MC for adequate follow-up as required by this protocol.
- •Patients must have normal organ function and adequate bone marrow reserve as assessed by the following laboratory requirements:
- •absolute neutrophil count >1.5 * 10^9/l;
- •platelet count >100*10^9/l;
- •Hb>6.0mmol/l;
- •Bilirubin < 1.5x upper limit of normal (ULN);
- •Serum aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2.5 x ULN;
- •Glomerular Filtration Rate (GFR) >45 and Creatinine clearance <2 x ULN.
排除标准
- •Medical or psychological impediment to probable compliance with the protocol.
- •Serious concomitant disease or active infections.
- •Distant metastasis other than peritoneal metastasis or metastatic lymph nodes.
- •No sufficient oral food intake.
- •Polyneuropathy grade 2 or worse according to CTCAE version 5.
- •History of auto-immune disease or organ allografts, or with active or chronic infection, including HIV and viral hepatitis.
- •Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for participation in this study.
- •Homozygous UGT1A1*28 genotype.
- •Homozygous dihydropyrimidine dehydrogenase (DPYD) genotype (tested for *2A, *13, 2846A>T, and 1236G>A).
- •Current use of strong CYP3A4-inhibitors or inducers. If patients use this CYP3A4-modulating medication, it is allowed to stop it within 14 days of start of treatment.
- •Pregnant or lactating women.
- •Concomitant participation in a competing clinical study.
- •Absence of assurance of compliance with the protocol.
- •An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.
研究组 & 干预措施
Intraperitoneal irinotecan 50 mg + CAPOX
Intraperitoneal irinotecan, dose level 1 50 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
Intraperitoneal irinotecan 50 mg + CAPOX
Intraperitoneal irinotecan, dose level 1 50 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 75 mg + CAPOX
Intraperitoneal irinotecan, dose level 2 75 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 75 mg + CAPOX
Intraperitoneal irinotecan, dose level 2 75 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
Intraperitoneal irinotecan 100 mg + CAPOX
Intraperitoneal irinotecan, dose level 3 100 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 100 mg + CAPOX
Intraperitoneal irinotecan, dose level 3 100 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
Intraperitoneal irinotecan 150 mg + CAPOX
Intraperitoneal irinotecan, dose level 4 150 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 150 mg + CAPOX
Intraperitoneal irinotecan, dose level 4 150 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
Intraperitoneal irinotecan 200 mg + CAPOX
Intraperitoneal irinotecan, dose level 5 200 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 200 mg + CAPOX
Intraperitoneal irinotecan, dose level 5 200 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
Intraperitoneal irinotecan 250 mg + CAPOX
Intraperitoneal irinotecan, dose level 6 250 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: Irinotecan (Drug)
Intraperitoneal irinotecan 250 mg + CAPOX
Intraperitoneal irinotecan, dose level 6 250 mg flat dose + oral capecitabine and systemic oxaliplatin (CAPOX) (dose via standard of care)
干预措施: CAPOX (Drug)
结局指标
主要结局
Maximum-tolerated dose
时间窗: 18 weeks
The maximum tolerable dose and recommended phase II dose of intraperitoneal irinotecan added to systemic chemotherapy (capecitabine/oxaliplatin)
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(18 weeks)
- Area Under the Curve (AUC) ratio intraperitoneal/systemic irinotecan(3 weeks)
研究者
Prof. R.H.J. Mathijssen, MD, PhD
Principal Investigator
Erasmus Medical Center