Organoids From Colorectal Peritoneal Metastases to Improve Cytoreductive Surgery and Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- One-year peritoneal metastasis-free survival
研究概览
简要总结
The objective of this clinical trial is to demonstrate that cytoreductive surgery and patient-tailored hyperthermic intra-peritoneal chemotherapy (HIPEC) will increase efficacy in controlling peritoneal disease. Tridimensional cell cultures (organoids) derived from colorectal cancer peritoneal metastases are used to select the most active drugs in an in vitro HIPEC model on individual-patient level, based on the hypothesis that resistance to drug(s) routinely used for intraperitoneal delivery can explain peritoneal relapse after combined treatment, depending on the individual tumor biology;
详细描述
This single-arm, single-center, open-label trial enrolls patients with limited and surgically resectable peritoneal metastases from colorectal cancer, no distant metastases, and no contraindication to major surgery. After signature of informed consent, patients undergo a preliminary laparoscopy to confirm diagnosis of peritoneal metastases, stage the disease, and obtain representative samples of peritoneal metastases. The investigators will use patient-derived organoids to select tailored hyperthermic intra-peritoneal chemotherapy (HIPEC) regimens in an in vitro model HIPEC. A set of candidate drugs suitable for intraperitoneal administration are tested on tumor-derived organoids under the same conditions as in the clinical practice (same drug combinations, concentration, exposure time, temperature). Different concentrations are tested to generate reproducible dose-response curves. Patients receive 3-6 month preoperative systemic chemotherapy with targeted agents, according to current guidelines. Those not experiencing disease progression during preoperative systemic chemotherapy will have cytoreductive surgery and HIPEC with drugs selected on the organoid-based preclinical model. Patients will undergo postoperative follow-up.
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
- •diagnosis of peritoneal metastases from intestinal-type or mucinous colo-rectal adenocarcinoma, by histological/cytological confirmation.
- •limited to moderate peritoneal involvement: peritoneal cancer index (PCI) ≤ 20;
- •peritoneal disease potentially amenable to complete surgical cytoreduction;
- •no evidence of hepatic, extra-regional nodal, or extra abdominal metastases
- •World Health Organization (WHO) performance status ≤2;
- •willingness to undergo preliminary laparoscopy, perioperative s-CT, and post-operative follow-up;
- •signature of informed consent.
排除标准
- •active sepsis;
- •impaired cardiac function (history of previous heart failure or 40% ejection fraction);
- •impaired renal function (serum creatinine >1.5 normal value or creatinine clearance < 60 ml/min);
- •impaired liver function (aspartate aminotransferase, alanine aminotransferase, bilirubin > 1.5 normal value);
- •impaired bone marrow function (leukocytes <4000/mm3, neutrophils <1500/mm3, platelets <80000/mm3);
- •impaired lung function (diagnosis of severe chronic obstructive pulmonary disease or 50% forced expiratory volume at one second or 40% diffusion capacity of lung for carbon monoxide adjusted for age);
- •dehydropyrimidine dehydrogenase deficiency;
- •pregnancy or lactation in progress;
- •haemorrhagic diathesis or coagulopathy;
- •any other condition or comorbidity that prevents safe administration of systemic chemotherapy (e.g. severe diarrhea, stomatitis or ulceration in the mouth or gastrointestinal tract);
- •psychiatric or neurological conditions that preclude the procedures of the protocol;
- •any contraindication to laparoscopy;
- •known hypersensitivity to any of the chemotherapy agents used for HIPEC in the present study and/or to any of their excipients;
- •history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma;
- •previous cytoreductive surgery and HIPEC
结局指标
主要结局
One-year peritoneal metastasis-free survival
时间窗: 12 months
Proportion of patients who remain free of peritoneal metastasis at a time interval of one year from the date of the combined procedure of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
次要结局
- Overall survival(60 months)
- Feasibility of patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)(48 months)
- Safety of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)(48 months)
- Disease-free survival(60 months)