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Trial record 1 of 1 for:    NCT02231086
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Adjuvant HIPEC in High Risk Colon Cancer (COLOPEC)

This study is currently recruiting participants.
See Contacts and Locations
Verified September 2016 by P.J. Tanis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Health Care Insurance Board
Information provided by (Responsible Party):
P.J. Tanis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT02231086
First received: August 22, 2014
Last updated: September 15, 2016
Last verified: September 2016
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms Peritoneal Neoplasms Procedure: Adjuvant HIPEC (open/laparoscopic) Drug: Standard adjuvant systemic chemotherapy Procedure: Diagnostic laparoscopy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Colon Cancer at High Risk of Peritoneal Carcinomatosis

Further study details as provided by P.J. Tanis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Peritoneal recurrence free survival [ Time Frame: 18 months ]
    Peritoneal recurrence-free survival at 18 months determined by CT and if negative by laparoscopy.


Secondary Outcome Measures:
  • Treatment related toxicity of adjuvant HIPEC, including 30-day complication rate, re-intervention rate, and re-admission rate [ Time Frame: 5 years ]
  • 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 ]
    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.

  • 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 [ Time Frame: 5 years ]

Estimated Enrollment: 176
Study Start Date: March 2015
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: 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.
Other Names:
  • adjuvant capecitabine and oxaliplatin (CAPOX)
  • adjuvant 5-FU and oxaliplatin (FOLFOX)
Procedure: 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 Name: Diagnostic laparoscopic surgery
Experimental: 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.
Procedure: 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.
Other Names:
  • 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)
Drug: 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.
Other Names:
  • adjuvant capecitabine and oxaliplatin (CAPOX)
  • adjuvant 5-FU and oxaliplatin (FOLFOX)
Procedure: 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 Name: Diagnostic laparoscopic surgery

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02231086

Contacts
Contact: Lotje Klaver, M.D. C.E.Klaver@amc.nl
Contact: Gijsbert Musters, M.D. +31-20-569111 ext 59507 G.D.Musters@amc.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Lotje E. Klaver, M.D.       C.E.Klaver@amc.nl   
Contact: Gijsbert D. Musters, M.D.       g.d.musters@amc.nl   
Principal Investigator: Pieter J Tanis, M.D., Ph.D.         
Sub-Investigator: W. A. Bemelman, M.D., Ph.D.         
Sub-Investigator: C JA Punt         
Antoni van Leeuwenhoek hospital Recruiting
Amsterdam, Netherlands
Contact: A Aalbers, M.D.         
Principal Investigator: A Aalbers         
Free University Medical Center Recruiting
Amsterdam, Netherlands
Contact: E A te Velde         
Principal Investigator: E A te Velde         
Sub-Investigator: W JH Meijerink         
Catharina hospital Recruiting
Eindhoven, Netherlands
Contact: I HJ de Hingh         
Principal Investigator: I HJ de Hingh         
University Medical Centre Groningen Recruiting
Groningen, Netherlands
Contact: R J van Ginkel         
Principal Investigator: R J van Ginkel         
Antonius hospital Recruiting
Nieuwegein, Netherlands
Contact: B van Ramshorst         
Principal Investigator: B van Ramshorst         
Radboud University Medical Center Recruiting
Nijmegen, Netherlands
Contact: A Bremers         
Principal Investigator: A Bremers         
Sub-Investigator: S A Radema         
Erasmus Medical Center Recruiting
Rotterdam, Netherlands
Contact: J WA Burger         
Principal Investigator: J WA Burger         
University Medical Center Utrecht Not yet recruiting
Utrecht, Netherlands
Contact: W MU van Grevenstein         
Principal Investigator: W MU van Grevenstein         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Health Care Insurance Board
Investigators
Principal Investigator: Pieter J. Tanis, M.D., Ph.D. Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: P.J. Tanis, M.D. Ph.D, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02231086     History of Changes
Other Study ID Numbers: NL49960.018.14
2014-002794-11 ( EudraCT Number )
Study First Received: August 22, 2014
Last Updated: September 15, 2016

Keywords provided by P.J. Tanis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Chemotherapy, Adjuvant
Laparoscopy
Peritoneal Lavage
HIPEC

Additional relevant MeSH terms:
Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Peritoneal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Abdominal Neoplasms
Peritoneal Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017