Phase IV Multicentric Clinical Trial to Evaluate the Efficacy of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Mytomicin-C After Complete Surgical Cytoreduction in Patients with Colon Cancer Peritoneal Metastases
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 216
- 试验地点
- 31
- 主要终点
- Peritoneal Recurrence Free Survival
研究概览
简要总结
The aim of this study is to assess whether there are differences in PERITONEAL RECURRENCE in patients with Colon Cancer Peritoneal Metastases treated with complete surgical resection and systemic chemotherapy, with (Group 1) or without (Group 2) HIPEC with Mitomycin-C.
详细描述
CytoReductive Surgery (CRS) + Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), especially from the year 2000 onwards, has obtained unprecedented results in patients with low to moderate volume peritoneal metastases (PM) of colorectal cancer (CRC), so that it has gradually been accepted, even being considered the best treatment for these patients. However, the actual role of HIPEC as a necessary component of treatment is unknown, despite its proven experimental basis. The French PRODIGE 7 study, presented at ASCO in 2018 and published on January 2021, has raised doubts about the survival benefit of HIPEC. In this study, there was no difference in overall survival (OS) with or without HIPEC (with Oxaliplatin 30 minutes) after resection of PM-CRC. However, since its presentation, several methodological flaws have been identified: a short exposure time to Oxaliplatin, an overestimation of the effect of HIPEC on OS (18 months) considered for the sample calculation, or the choice of OS as the main endpoint (since HIPEC can reduce peritoneal relapses, while OS is also influenced by the systemic treatment received by all patients). Due to these shortcomings and some others, the results have not been assumed to be definitive. Therefore, the majority of units specialized in peritoneal surface malignancy, continue to consider HIPEC in these patients as a recommended option, usually changing Oxaliplatin for Mitomycin-C (MMC). With these premises we propose this multicenter Clinical Trial, correcting the retrospective defects of PRODIGE 7. To do this, the cytostatic used in HIPEC will be changed (MMC instead of oxaliplatin), the infusion time will be increased (from 30 to 90 minutes), rectal cancers are ruled out (only colon cancers will be included), cases with high peritoneal extension (PCI> 20) will be avoided, those cases in which a complete CRS (CCS 0) is not achieved will be excluded, and the main objective will be the Peritoneal Recurrence Free Survival (RFS) instead of the OS.
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 colon adenocarcinoma, except signet ring cell carcinomas (those with > 50% of the tumor composed of these cells, which comprise only 1% of all colon adenocarcinomas).
- •Absence of previously treated or current extraperitoneal metastases, including distant lymphadenopathy (retroperitoneal, mediastinal, etc), liver metastases, or lung metastases (ruled out by PET-scan in case of doubt).
- •Synchronous or metachronous peritoneal metastasis of mild to moderate volume, with a PCI ≤ 20 (Appendix 2) (intraoperative confirmation).
- •Macroscopically complete surgical cytoreduction CCS-0 (intraoperative confirmation).
- •Treatment with perioperative systemic chemotherapy (SCT), before and/or after surgical procedure.
- •Age> 18 years.
- •Acceptable anesthetic/surgical risk: ASA 1-3 (Appendix 3), ECOG 0-1 (Appendix 4). No severe alterations in hematological, renal, cardiac, pulmonary or hepatic function (operable patients).
- •Information to the patient and signing of a study-specific informed consent.
排除标准
- •Peritoneal carcinomatosis of any other origin, particularly rectal cancer or appendicular adenocarcinoma, or signet ring cell colon cancer on histology.
- •No intraoperative confirmation of peritoneal disease (PCI 0). Likewise, cases of perianastomotic (local) or lymph node (locoregional) recurrences will be excluded.
- •High volume peritoneal disease with a PCI> 20 (intraoperative evaluation).
- •Concurrent or previously treated extraperitoneal disease.
- •Disease progression during preoperative chemotherapy, if received.
- •Patients previously treated with HIPEC.
- •History of other cancers (except cutaneous basal cell carcinoma or cervix carcinoma in situ) in the 5 years prior to entry into the study.
- •Patients included in another first-line clinical trial for the studied disease.
- •Pregnancy (or suspicion of it) or lactation period.
- •Emergency surgical intervention for obstruction or perforation of a primary tumour with synchronous PM (although rescue and secondary CRS + HIPEC after emergency surgery of the primary tumour are acceptable if inclusion criteria are fulfilled).
- •Persons deprived of liberty or under legal or administrative supervision.
- •Inability to understand the nature of the intervention, the risks, benefits, expected evolution and the need to undergo periodic medical examinations, either for geographical, social or psychological reasons.
研究组 & 干预措施
complete cytoreductive surgery plus HIPEC with Mytomicin C for 90 minutes
干预措施: complete cytoreductive surgery plus HIPEC with Mytomicin C for 90 minutes (Drug)
complete cytoreductive surgery without HIPEC
干预措施: complete cytoreductive surgery without HIPEC (Procedure)
结局指标
主要结局
Peritoneal Recurrence Free Survival
时间窗: 3 years
From the date of surgery to the date of peritoneal recurrence or death, or to the end of follow-up
次要结局
- Global recurrence at any location (Disease Free Survival)(3 years)
- Locoregional and distant recurrence rate (isolated or coincident, with or without simultaneous peritoneal recurrence)(3 years)
- Postoperative complications (rate and severity grade)(days 1-90 after surgery)
- Peritoneal and global recurrence rate according to stratified PCI(3 years)
- Overall survival(3 years)
- Quality of Life with EORTC validated questionnaire Colorectal Cancer Module (QLQ-CR29).(pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months)
- Quality of Life with EORTC validated questionnaire Core 30 (QLQ-C30)(pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months)
研究者
Fernando Pereira
Principal Investigator, Head of Surgery Dpt, Clinical Professor
Hospital Universitario de Fuenlabrada