Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
204 participants
INTERVENTIONAL
2015-03-31
2019-06-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Cytoreduction Followed by Normothermic Versus Hyperthermic Intraperitoneal Intraoperative Chemoperfusion (HIPEC): a Study in Peritoneal Carcinomatosis
NCT01575730
Adjuvant HIPEC to Prevent Colorectal Peritoneal Metastases in High-risk Patients
NCT02575859
Prophylactic HIPEC for Colorectal Cancers at High Risk of Developing Peritoneal Metastases
NCT03422432
Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases
NCT02758951
Radical Colorectal Resection and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Locally Advanced Colorectal Cancer
NCT02830139
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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:
Patients who underwent intentionally curative resection for a T4N0-2M0 or intra-abdominally perforated colon cancer.
Intervention:
Adjuvant HIPEC procedure: access to the abdominal cavity by laparoscopy or laparotomy under general anaesthesia, adhesiolysis if necessary, complete staging of the intra-abdominal cavity, positioning of in- and outflow catheters, perfusion with a minimum of 2l isotonic dialysis fluid at a flow rate of 1-2l/min and an inflow temperature of 42-43˚C. Before the beginning of HIPEC, 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 will be administered intravenously to potentiate oxaliplatin activity. Oxaliplatin (460 mg/m2) is added to the perfusate after attaining at least 42 degrees inflow temperature with a total of 30 minutes perfusion time.
Outcomes:
Primary endpoint is peritoneal recurrence-free survival at 18 months. Secondary endpoints are number of participants with adverse events as a measure of safety and tolerability, incidence of PC at end of follow-up with or without concomitant liver/lung metastases, percentage of false negative CT at 18 months (second look laparoscopy/laparotomy as gold standard), disease-free survival, overall survival, quality of life and costs.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Standard adjuvant systemic chemotherapy
Colon cancer patients with a high risk of developing PC, but do not have (yet) proven macroscopic peritoneal metastasis, are standardly treated with adjuvant systemic chemotherapy. Standard adjuvant systemic chemotherapy consists in the Netherlands of a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) for a total of 6 months.
Diagnostic laparoscopy
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 in both study arms.
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.
Adjuvant HIPEC (open/laparoscopic)
Adjuvant HIPEC procedure: access to the abdominal cavity by laparoscopy or laparotomy under general anaesthesia, adhesiolysis if necessary, complete staging of the intra-abdominal cavity, positioning of in- and outflow catheters, perfusion with a minimum of 2l isotonic dialysis fluid at a flow rate of 1-2l/min and an inflow temperature of 42-43˚C. Before the beginning of HIPEC, 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 will be administered intravenously to potentiate oxaliplatin activity. Oxaliplatin (460 mg/m2) is added to the perfusate after attaining at least 42 degrees inflow temperature with a total of 30 minutes perfusion time.
Standard adjuvant systemic chemotherapy
Colon cancer patients with a high risk of developing PC, but do not have (yet) proven macroscopic peritoneal metastasis, are standardly treated with adjuvant systemic chemotherapy. Standard adjuvant systemic chemotherapy consists in the Netherlands of a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) for a total of 6 months.
Diagnostic laparoscopy
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 in both study arms.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Adjuvant HIPEC (open/laparoscopic)
Adjuvant HIPEC procedure: access to the abdominal cavity by laparoscopy or laparotomy under general anaesthesia, adhesiolysis if necessary, complete staging of the intra-abdominal cavity, positioning of in- and outflow catheters, perfusion with a minimum of 2l isotonic dialysis fluid at a flow rate of 1-2l/min and an inflow temperature of 42-43˚C. Before the beginning of HIPEC, 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 will be administered intravenously to potentiate oxaliplatin activity. Oxaliplatin (460 mg/m2) is added to the perfusate after attaining at least 42 degrees inflow temperature with a total of 30 minutes perfusion time.
Standard adjuvant systemic chemotherapy
Colon cancer patients with a high risk of developing PC, but do not have (yet) proven macroscopic peritoneal metastasis, are standardly treated with adjuvant systemic chemotherapy. Standard adjuvant systemic chemotherapy consists in the Netherlands of a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) for a total of 6 months.
Diagnostic laparoscopy
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 in both study arms.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
Exclusion Criteria
* 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.
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
ZonMw: The Netherlands Organisation for Health Research and Development
OTHER
Dutch Health Care Insurance Board
OTHER
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
P.J. Tanis
M.D. Ph.D
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pieter J. Tanis, M.D., Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Academic Medical Center
Amsterdam, , Netherlands
Antoni van Leeuwenhoek hospital
Amsterdam, , Netherlands
Free University Medical Center
Amsterdam, , Netherlands
Catharina hospital
Eindhoven, , Netherlands
University Medical Centre Groningen
Groningen, , Netherlands
Antonius hospital
Nieuwegein, , Netherlands
Radboud University Medical Center
Nijmegen, , Netherlands
Erasmus Medical Center
Rotterdam, , Netherlands
University Medical Center Utrecht
Utrecht, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Zwanenburg ES, Wisselink DD, Klaver CEL, Bilt JDWV, den Berg JGV, Kodach LL, Nagtegaal ID, Tanis PJ, Snaebjornsson P; COLOPEC collaborators. Underdiagnosis of positive resection margins and synchronous peritoneal metastases in locally advanced colon cancer: histopathological reassessment of primary resection in the COLOPEC trial. Virchows Arch. 2025 May 16. doi: 10.1007/s00428-025-04065-x. Online ahead of print.
Zwanenburg ES, El Klaver C, Wisselink DD, Punt CJA, Snaebjornsson P, Crezee J, Aalbers AGJ, Brandt-Kerkhof ARM, Bremers AJA, Burger PJWA, Fabry HFJ, Ferenschild FTJ, Festen S, van Grevenstein WMU, Hemmer PHJ, de Hingh IHJT, Kok NFM, Kusters M, Musters GD, Schoonderwoerd L, Tuynman JB, van de Ven AWH, van Westreenen HL, Wiezer MJ, Zimmerman DDE, van Zweeden A, Dijkgraaf MGW, Tanis PJ; COLOPEC Collaborators Group; COLOOPEC Collaborators Group. Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial. J Clin Oncol. 2024 Jan 10;42(2):140-145. doi: 10.1200/JCO.22.02644. Epub 2023 Nov 3.
Zwanenburg ES, Wisselink DD, Klaver CEL, van der Bilt JDW, Tanis PJ, Snaebjornsson P; COLOPEC trial collaborators. The measured distance between tumor cells and the peritoneal surface predicts the risk of peritoneal metastases and offers an objective means to differentiate between pT3 and pT4a colon cancer. Mod Pathol. 2022 Dec;35(12):1991-2001. doi: 10.1038/s41379-022-01154-z. Epub 2022 Sep 19.
Klaver CEL, Wisselink DD, Punt CJA, Snaebjornsson P, Crezee J, Aalbers AGJ, Brandt A, Bremers AJA, Burger JWA, Fabry HFJ, Ferenschild F, Festen S, van Grevenstein WMU, Hemmer PHJ, de Hingh IHJT, Kok NFM, Musters GD, Schoonderwoerd L, Tuynman JB, van de Ven AWH, van Westreenen HL, Wiezer MJ, Zimmerman DDE, van Zweeden AA, Dijkgraaf MGW, Tanis PJ; COLOPEC collaborators group. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol. 2019 Oct;4(10):761-770. doi: 10.1016/S2468-1253(19)30239-0. Epub 2019 Jul 29.
Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, Aalbers AG, van der Bilt JD, Boerma D, Bremers AJ, Burger JW, Buskens CJ, Evers P, van Ginkel RJ, van Grevenstein WM, Hemmer PH, de Hingh IH, Lammers LA, van Leeuwen BL, Meijerink WJ, Nienhuijs SW, Pon J, Radema SA, van Ramshorst B, Snaebjornsson P, Tuynman JB, Te Velde EA, Wiezer MJ, de Wilt JH, Tanis PJ. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer. 2015 May 24;15:428. doi: 10.1186/s12885-015-1430-7.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2014-002794-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NL49960.018.14
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.