Phase II Multicenter Randomized Trial Evaluating the Association of PIPAC and Systemic Chemotherapy Versus Systemic Chemotherapy Alone as 1st-line Treatment of Malignant Peritoneal Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- overall survival
研究概览
简要总结
MESOTIP is a randomized trial evaluating the association of PIPAC and systemic chemotherapy versus systemic chemotherapy alone as 1st-line treatment of Malignant Peritoneal Mesothelioma In this study, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed).
MESOTIP aim to show an improvement of the overall survival in the experimental arm.
详细描述
Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The incidence of all mesotheliomas is estimated quite differently in various reports with the highest rates in industrialized countries. In France, the estimated incidence is 300 cases/year. Three types of malignant mesotheliomas are described in the WHO classification: epithelioid, sarcomatoid and biphasic.
The standard treatment of MPM is surgery. It has been shown that cytoreductive surgery (CRS) associated to hyperthermic intraperitoneal chemotherapy (HIPEC) improves prognosis resulting in a median overall survival of 29.5 months to 53 months and an 5 years overall survival rate ranging between 39 to 63%. Cytoreductive surgery should be complete or almost complete (CCR0/1) as macroscopic residual disease deteriorates prognosis.
However some patients are not eligible for surgery due to the locoregional extension of the disease. Although debulking surgery may still be considered, its results are less encouraging than CRS and HIPEC.
The neoadjuvant treatment combining Cisplatin and Pemetrexed became a routinely applied option for initially unresectable patients after the publication of an open-label study inspired by previous results of a randomized trial in pleural mesothelioma. This study showed a benefit in median survival of 5 months and an increase in the response rate of 10%. Ever since, other phase II studies were proposed but their benefit is still limited. Pleural mesothelioma which is more common and represents the model of choice for the treatment of peritoneal mesothelioma has also benefitted from phase III studies analyzing the addition of a targeted therapy (Bevacizumab) and phase II trials proposing immunotherapy.
By contrast, peritoneal mesothelioma was the setting of choice for testing intraperitoneal administration of chemotherapy either as early postoperative intraperitoneal chemotherapy (EPIC) or as neoadjuvant intraperitoneal chemotherapy. Both studies offered promising results showing a sensitivity of MPM to intraperitoneal administration.
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
- •Age ≥ 18 years
- •PS (or WHO) <2
- •Histologically-confirmed diagnosis of peritoneal malignant mesothelioma
- •No previous line of treatment (both medical and surgical oncologic treatments) for this disease
- •Peritoneal Carcinomatosis Index (PCI)>27 or at least 4 on the small bowel with serosal involvement contraindicating the cytoreductive surgery because of the impossibility to preserve a length >=1.5 m of uninvolved small bowel
- •Written and dated informed consent
- •Affiliated to the French national social security system
排除标准
- •WHO performance status ≥ 2
- •Any contraindication to chemotherapy and/or radiotherapy
- •Any contraindication to repeated laparoscopy
- •Symptomatic cardiac or coronary insufficiency
- •Severe renal insufficiency
- •Progressive active infection or any other severe medical condition
- •Intestinal occlusion non responsive to medical treatment
- •Other cancer treated within the last 2 years except in situ cervical carcinoma or basocellular/spinocellular carcinoma
- •Pregnant or breast-feeding woman
- •Previously operated patients where laparoscopy is not feasible
- •Persons deprived of liberty or under guardianship or incapable of giving consent
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
研究组 & 干预措施
association of PIPAC and systemic chemotherapy
4 PIPAC of Cisplatin 10.5mg/m² + Doxorubicin 2.1 mg/m² every 6 weeks alternating with standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
干预措施: PIPAC (Procedure)
association of PIPAC and systemic chemotherapy
4 PIPAC of Cisplatin 10.5mg/m² + Doxorubicin 2.1 mg/m² every 6 weeks alternating with standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
干预措施: Cisplatin (Drug)
association of PIPAC and systemic chemotherapy
4 PIPAC of Cisplatin 10.5mg/m² + Doxorubicin 2.1 mg/m² every 6 weeks alternating with standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
干预措施: Pemetrexed (Drug)
systemic chemotherapy alone
6 cycles of Cisplatin 75mg/m² + Pemetrexed 500mg/m²
干预措施: Cisplatin (Drug)
systemic chemotherapy alone
6 cycles of Cisplatin 75mg/m² + Pemetrexed 500mg/m²
干预措施: Pemetrexed (Drug)
结局指标
主要结局
overall survival
时间窗: from randomization of first patient until the database cut-off
The overall survival is defined as the time from the date of randomization to the date of death from any cause
次要结局
- Conversion to resectability(surgery)
- Response to treatment using PFS(week 10, week21,every 4 months during 2 years)
- Adverse event(during treatment)
- Quality of life evaluation(baseline, week10, week21, FU every 4 months during 2 years)
- Feasibility of compliance(Week 21)