Colorectal NeoplasmsPhase 3COLOPECNCT02231086
Adjuvant HIPEC in High Risk Colon Cancer
A Phase 3 study testing Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy and Diagnostic laparoscopy in people with Colorectal Neoplasms and Peritoneal Neoplasms, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 9 sites in Netherlands.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms, Peritoneal Neoplasms
- What is being tested?
- Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy and Diagnostic laparoscopy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 9 sitesNetherlands
- Study dates
- Mar 2015to 1 Jun 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Netherlands9 sites
Academic Medical Center
Amsterdam, 1105 AZ
Antoni van Leeuwenhoek hospital
Amsterdam
Free University Medical Center
Amsterdam
Catharina hospital
Eindhoven
University Medical Centre Groningen
Groningen
Antonius hospital
Nieuwegein
Radboud University Medical Center
Nijmegen
Erasmus Medical Center
Rotterdam
University Medical Center Utrecht
Utrecht
About this study
Official title: Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Colon Cancer at High Risk of Peritoneal Carcinomatosis
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.
Read the detailed description
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:
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
- Colorectal Neoplasms, Peritoneal Neoplasms
- Being tested
- Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy, Diagnostic laparoscopy
- Keywords
- Chemotherapy, Adjuvant, Laparoscopy, Peritoneal Lavage, HIPEC
- Medical subject headings
- Colorectal Neoplasms, Peritoneal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvant HIPEC (open/laparoscopic)Procedure or surgery
Also called I.V. leucovorin 20 mg/m2 (maximum 40 mg), I.V. 5-fluorouracil 400 mg/m2 (maximum 800 mg), Intraperitoneal oxaliplatin 460 mg/m2 (maximum 920 mg)
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 chemotherapyDrug
Also called adjuvant capecitabine and oxaliplatin (CAPOX), adjuvant 5-FU and oxaliplatin (FOLFOX)
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 laparoscopyProcedure or surgery
Also called Diagnostic laparoscopic surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard adjuvant systemic chemotherapy | Active comparator | 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. Receives: Drug: Standard adjuvant systemic chemotherapy; Procedure: Diagnostic laparoscopy |
| Adjuvant HIPEC (open/laparoscopic) | Experimental | 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. Receives: Procedure: Adjuvant HIPEC (open/laparoscopic); Drug: Standard adjuvant systemic chemotherapy; Procedure: Diagnostic laparoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peritoneal Recurrence Free Survival at 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.
Measured: 18 months
Secondary outcomes (7)
Treatment Related Toxicity of Adjuvant HIPEC
Toxicity directly related to adjuvant HIPEC included 30-day complication rate, re-intervention rate, and re-admission rate.
Measured: 30 days after adjuvant HIPEC
Hospital Stay for Simultaneous and Staged HIPEC, Either Open or Laparoscopic
Hospital stay for simultaneous and staged HIPEC, either open or laparoscopic.
Measured: 10 weeks
False-negative Rate of CT-scan for Peritoneal Metastases
The presence or absence of peritoneal metastasis on CT-scan will be compared to the findings during diagnostic laparoscopy, histological biopsy or fine needle aspiration cytology.
Measured: 5 years
Patterns of Dissemination (Peritoneal Plus or Minus Distant Metastases)
Patterns of dissemination (peritoneal plus or minus distant metastases).
Measured: 5 years
Disease-free Survival
Disease-free survival.
Measured: 5 years
Overall Survival
Overall survival.
Measured: 5 years
Quality of Life Questionnaire Survey 5- Year Follow-up
Quality of life questionnaire survey 5- year follow-up.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2014 (estimated)
- Study startMar 2015
- Primary completionSep 2018
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 204 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Health Care Insurance Board
- Responsible party
- Principal investigator, P.J. Tanis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Pieter J. Tanis, M.D., Ph.D., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02231086
- Sponsor's protocol ID
- NL49960.018.14
- Other IDs
- 2014-002794-11, 2014
- Acronym
- COLOPEC
- Status last verified
- Aug 2021
- First submitted
- 22 Aug 2014
- Last updated
- 16 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 Oct;487(4):787-797. doi: 10.1007/s00428-025-04065-x. Epub 2025 May 16.
PubMed 40374989Zwanenburg 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.
PubMed 37922442Zwanenburg 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.
PubMed 36123540Klaver 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.
PubMed 31371228Klaver 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.
PubMed 26003804
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Colon Cancer at High Risk of Peritoneal Carcinomatosis
- ClinicalTrials.gov ID
- NCT02231086
- Acronym / sponsor ID
- COLOPEC / NL49960.018.14
- Conditions
- Colorectal Neoplasms, Peritoneal Neoplasms
- Keywords
- Chemotherapy, Adjuvant, Laparoscopy, Peritoneal Lavage, HIPEC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 204 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Health Care Insurance Board
- Study start
- Mar 2015 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 4 Sep 2014 (estimated)
- Results
- Posted 16 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard adjuvant systemic chemotherapy | Active comparator | Drug: Standard adjuvant systemic chemotherapy, Procedure: Diagnostic laparoscopyStandard 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. |
| Adjuvant HIPEC (open/laparoscopic) | Experimental | Procedure: Adjuvant HIPEC (open/laparoscopic), Drug: Standard adjuvant systemic chemotherapy, Procedure: Diagnostic laparoscopyAdjuvant 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adjuvant HIPEC (open/laparoscopic)Also: I.V. leucovorin 20 mg/m2 (maximum 40 mg), I.V. 5-fluorouracil 400 mg/m2 (maximum 800 mg), Intraperitoneal oxaliplatin 460 mg/m2 (maximum 920 mg)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. | Procedure or surgery | Adjuvant HIPEC (open/laparoscopic) |
| Standard adjuvant systemic chemotherapyAlso: adjuvant capecitabine and oxaliplatin (CAPOX), adjuvant 5-FU and oxaliplatin (FOLFOX)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. | Drug | Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy |
| Diagnostic laparoscopyAlso: Diagnostic laparoscopic surgeryPresence 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. | Procedure or surgery | Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy |
Primary outcome
Peritoneal Recurrence Free Survival at 18 Months
Time frame: 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.
7 secondary outcomes
Treatment Related Toxicity of Adjuvant HIPEC
Time frame: 30 days after adjuvant HIPEC
Hospital Stay for Simultaneous and Staged HIPEC, Either Open or Laparoscopic
Time frame: 10 weeks
False-negative Rate of CT-scan for Peritoneal Metastases
Time frame: 5 years
Patterns of Dissemination (Peritoneal Plus or Minus Distant Metastases)
Time frame: 5 years
Disease-free Survival
Time frame: 5 years
Overall Survival
Time frame: 5 years
Quality of Life Questionnaire Survey 5- Year Follow-up
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40374989Zwanenburg 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 Oct;487(4):787-797. doi: 10.1007/s00428-025-04065-x. Epub 2025 May 16.
- Derived from this study: PubMed 37922442Zwanenburg 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.
- Derived from this study: PubMed 36123540Zwanenburg 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.
- Derived from this study: PubMed 31371228Klaver 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.
- Derived from this study: PubMed 26003804Klaver 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pieter J. Tanis, M.D., Ph.D. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adjuvant HIPEC (open/laparoscopic), Standard adjuvant systemic chemotherapy and Diagnostic laparoscopy in people with Colorectal Neoplasms and Peritoneal Neoplasms, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 9 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peritoneal Recurrence Free Survival at 18 Months (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02231086, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.