Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Colon Cancer at High Risk of Peritoneal Carcinomatosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 9
- 主要终点
- Peritoneal Recurrence Free Survival at 18 Months
研究概览
简要总结
This study aims to determine the oncological effectiveness of adjuvant HIPEC, using intraperitoneal oxaliplatin with concomitant i.v. 5-FU/LV, following a curative resection of a T4 or intra-abdominally perforated Colon cancer in preventing the development of peritoneal carcinomatosis in addition to the standard adjuvant systemic treatment.
Hypothesis:
The hypothesis is that adjuvant HIPEC preceding routine adjuvant systemic therapy using i.p. oxaliplatin with concomitant i.v. 5-FU/LV following a curative resection of a T4 or intra-abdominally perforated colon cancer reduces the development of peritoneal carcinomatosis in comparison to standard adjuvant systemic treatment alone.
详细描述
Background:
The peritoneum is the second most common site of recurrence in patients with colon cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult and adjuvant systemic treatment does not seem to affect peritoneal dissemination in contrast to haematogenous dissemination in the liver or lungs. Of all patients eventually presenting with clinically apparent PC, only a quarter have potentially curable disease. The curative option is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC), but the effectiveness depends highly on the extent of disease and is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant intraperitoneal therapy in high risk colon cancer patients in order to prevent the development of PC with treatment at a subclinical stage.
Study design:
This will be a multicentre study in which 176 eligible patients will be randomized to adjuvant HIPEC followed by adjuvant systemic chemotherapy in the experimental arm, or the standard adjuvant systemic chemotherapy alone in the control arm. Adjuvant HIPEC will be performed preferably simultaneously or within 10 days after resection of the primary tumour, either by laparoscopy or open approach, similar to the technique used for resection of the primary tumour. If adjuvant HIPEC cannot be performed within 10 days (i.e. complicated postoperative course), the procedure will be delayed until 5 to 8 weeks postoperatively. Subsequently, patients will receive routine adjuvant chemotherapy (CAPOX) within 3 weeks from HIPEC. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. If peritoneal carcinomatosis is found during staging laparoscopy, CR/ HIPEC will be performed in patients with a maximum of 5 involved regions and without evidence of systemic disease.
Study population:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •age between 18 and 75 years
- •Intention to start routine adjuvant systemic therapy
- •adequate clinical condition to undergo simultaneous HIPEC or re- laparoscopy or re-laparotomy with HIPEC within either 10 days or between week 5-8 from --primary resection
- •written informed consent
- •white blood cell count of at least 3000/mm3, platelet count of at least 100.000/mm3
- •no bleeding diathesis or coagulopathy
- •normal creatinine or creatinine clearance of at least 50 ml/min
排除标准
- •postoperative complications that interfere with adjuvant HIPEC within 8 weeks (i.e. persisting intra-abdominal abscess, significant fascial dehiscence, enteric fistula)
- •no intention to start routine adjuvant systemic therapy
- •liver and/or lung metastases
- •pregnant or lactating women
- •unstable or uncompensated respiratory or cardiac disease
- •serious active infections
- •other concurrent chemotherapy
- •hypersensitivity to fluorouracil, folinic acid or another substance of leucovorin or oxaliplatin
- •stomatitis, ulceration in the mouth or gastrointestinal tract.
- •severe diarrhea
- •severe hepatic and / or renal dysfunction.
- •plasma bilirubin concentrations greater than 85 μmol/l.
- •pernicious anemia or other anaemias due to vitamin B12 deficiency.
- •peripheral sensory neuropathy with functional impairment.
研究组 & 干预措施
Standard adjuvant systemic chemotherapy
Standard adjuvant systemic chemotherapy according to the Dutch colon cancer guideline, using a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) schedule. Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively.
干预措施: Standard adjuvant systemic chemotherapy (Drug)
Standard adjuvant systemic chemotherapy
Standard adjuvant systemic chemotherapy according to the Dutch colon cancer guideline, using a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) schedule. Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively.
干预措施: Diagnostic laparoscopy (Procedure)
Adjuvant HIPEC (open/laparoscopic)
Adjuvant HIPEC will be performed simultaneously with primary tumor resection, or as a staged procedure (<10 days or 5-8 weeks postoperatively). The chemotherapy during oxaliplatin-HIPEC consists of an intravenous phase with leucovorin 20 mg/m2 (maximum 40 mg) and 5-fluorouracil 400 mg/m2 (maximum 800 mg) and an intraperitoneal phase with oxaliplatin 460 mg/m2 (maximal 920 mg). Standard adjuvant systemic chemotherapy according to the national guideline will be given within 3 weeks from HIPEC. Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively.
干预措施: Adjuvant HIPEC (open/laparoscopic) (Procedure)
Adjuvant HIPEC (open/laparoscopic)
Adjuvant HIPEC will be performed simultaneously with primary tumor resection, or as a staged procedure (<10 days or 5-8 weeks postoperatively). The chemotherapy during oxaliplatin-HIPEC consists of an intravenous phase with leucovorin 20 mg/m2 (maximum 40 mg) and 5-fluorouracil 400 mg/m2 (maximum 800 mg) and an intraperitoneal phase with oxaliplatin 460 mg/m2 (maximal 920 mg). Standard adjuvant systemic chemotherapy according to the national guideline will be given within 3 weeks from HIPEC. Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively.
干预措施: Standard adjuvant systemic chemotherapy (Drug)
Adjuvant HIPEC (open/laparoscopic)
Adjuvant HIPEC will be performed simultaneously with primary tumor resection, or as a staged procedure (<10 days or 5-8 weeks postoperatively). The chemotherapy during oxaliplatin-HIPEC consists of an intravenous phase with leucovorin 20 mg/m2 (maximum 40 mg) and 5-fluorouracil 400 mg/m2 (maximum 800 mg) and an intraperitoneal phase with oxaliplatin 460 mg/m2 (maximal 920 mg). Standard adjuvant systemic chemotherapy according to the national guideline will be given within 3 weeks from HIPEC. Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively.
干预措施: Diagnostic laparoscopy (Procedure)
结局指标
主要结局
Peritoneal Recurrence Free Survival at 18 Months
时间窗: 18 months
Peritoneal recurrence-free survival at 18 months determined by CT and CEA. If CEA was normal and CT did not show any signs of peritoneal metastase at 18 months, a diagnostic laparoscopy was performed in those patients who consented to this intervention. Complete peritoneal staging was performed during laparoscopy, and biopsies were taken from suspicious lesions. If no peritoneal lesions were seen or biopsies were negative, this indicated that the patient was free from peritoneal recurrence.
次要结局
- Treatment Related Toxicity of Adjuvant HIPEC(30 days after adjuvant HIPEC)
- False-negative Rate of CT-scan for Peritoneal Metastases(5 years)
- Patterns of Dissemination (Peritoneal Plus or Minus Distant Metastases)(5 years)
- Hospital Stay for Simultaneous and Staged HIPEC, Either Open or Laparoscopic(10 weeks)
- Disease-free Survival(5 years)
- Overall Survival(5 years)
- Quality of Life Questionnaire Survey 5- Year Follow-up(5 years)
研究者
P.J. Tanis
M.D. Ph.D
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)