Cytoreductive Surgery Plus Hyperthermic Intraoperative Peritoneal Chemotherapy With Cisplatin to Treat Peritoneal Carcinomatosis From Upper Gastrointestinal Cancer; the HIPCUpp-trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Baki Topal
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Overall survival time (OS) following CRS+HIPC (from surgery to cancer-related death)
研究概览
简要总结
The majority of patients with upper gastrointestinal cancer, such as gastric, biliary, or pancreatic carcinoma, present with metastatic disease, and have an extremely poor survival, irrespective the type of treatment modality. The aim of the current monocentric phase II study is to evaluate in these patients the effectiveness of cytoreductive surgery (CRS) plus hyperthermic intraoperative peritoneal chemotherapy with cisplatin (HIPC). The study is designed to have at least 80% power to detect a 40% increase in 1-year overall survival common to all strata (gastric-biliary-pancreas) after CRS+HIPC. Over an anticipated period of 2 years, 60 patients will undergo CRS + HIPC. Translational research will quantify perioperative circulating and peritoneal tumour cells, based on real-time RT-PCR for CEA and EpCAM. Plasma concentration of cytokines will be determined for IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ, and VEGF at several time-points. Systemic immunological changes will be assessed by flow cytometric quantification of the relative proportions and absolute numbers of B- and T-lymphocytes, NK cells, effector T cells, HLA-DR+ T cells, and regulatory T cells. Gene-expression studies will be performed using Affymetrix HG U133 Plus 2.0 arrays on primary and metastatic tissue samples.
详细描述
ASSESSMENT of TUMOUR BURDEN • Tumour burden will be assessed using diagnostic imaging modalities and verified by surgical or laparoscopic evaluation before CRS+HIPC
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Primary tumour Biliary adenocarcinoma
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Intrahepatic cholangiocellular carcinoma < 3 cm in diameter
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Extrahepatic cholangiocellular carcinoma without invasion of major blood vessels (portal vein, hepatic arteries, coeliac trunk) Gastric adenocarcinoma Macroscopic surgical margin of 5 cm is needed to obtain complete tumour removal Pancreatic adenocarcinoma Tumours located in the head, body or tail of the pancreas without portal hypertension due to complete encasement of mesenteric/portal vein and collateral venous circulation
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Liver metastases
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Only liver metastases with stable disease or clinical response to prior systemic therapy for a period of at least 3 months are eligible
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Not more than 3 metastases, each measuring 3 cm or less in diameter
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Solitary liver metastasis smaller than 5 cm in diameter located in the periphery of ventral segments (Sg 2-6)
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Peritoneal metastases
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Sugarbaker's peritoneal cancer index (PCI) will be used to assess peritoneal tumour burden 28. The completeness of cancer resection (CCR) will be assessed by the surgeon at the end of CRS; CCR-0 no macroscopic residual tumour, CCR-1 no residual tumour nodules greater than 2.5 mm, CCR-2 residual tumour nodules larger than 2.5 mm in diameter.
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Patients with PCI < 20 are eligible for this study 11.
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
- •Primary or recurrent disease
- •Histological confirmation of primary (or recurrent) and metastatic disease
- •Systemic chemotherapy and/or biological is allowed before and/or after CRS+HIPC
- •Radiotherapy is allowed before or after CRS+HIPC
- •Patients must not have failed prior intraperitoneal platinum-therapy
- •Age between 18 to 75 years
- •Patient Karnofsky performance scale (KPS) > 80 (normal activity with a bit of effort)
排除标准
- •Age < 18 or > 75 years
- •Pregnancy
- •Any malignancy other than biliary, gastric, or pancreatic adenocarcinoma
- •Any metastatic disease outside the abdominal compartment, such as pulmonary or bone metastases
- •Peritoneal carcinomatosis index (PCI) > 20 at the start of CRS
- •Peritoneal residual tumour nodules larger than 2.5 mm after CRS (CCR-2)
- •Clinical relevant ascites
- •More than 3 liver metastases
- •Solitary liver metastasis larger than 5 cm
结局指标
主要结局
Overall survival time (OS) following CRS+HIPC (from surgery to cancer-related death)
时间窗: 1 year follow-up
Statistical methodology. The study is designed to have at least 80% power to detect a 40% increase in 1-y OS common to all strata (gastric-biliary-pancreas) after CRS+HIPC. The reference percentages 1-y OS are 52%, 37% and 34% for gastric, biliary and pancreatic cancer, respectively. An exponential distribution is assumed for the event times in the study group with a parameter yielding 72.8%, 51.8% and 47.6% 1-y OS in the mentioned strata. Cancer-specific survival will be monitored using consecutive CT- and/or MRI-scan every 3 months after CRS+HIPC.
次要结局
- In-hospital perioperative complications(up to 24 weeks)
研究者
Baki Topal
Professor of Surgery
University Hospital, Gasthuisberg