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RecruitingNCT03914820CHECKUpdated Oct 27, 2023

Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK Study.

An interventional study of HIPEC CO2 surgery and Standard surgery in Colorectal Neoplasms, sponsored by Mario Negri Institute for Pharmacological Research. Recruiting at 16 sites in Italy. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-10-27.

Sponsored by Mario Negri Institute for Pharmacological Research · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Jun 2025, 1 year 4 months ago, but the record still lists the study as recruiting.
  • Started Jun 2020; still recruiting 6 years 3 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
330
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a phase III randomized, multicenter study with two different arm:

  • experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin
  • comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility.

Patient will be randomized in a 1:1 ratio. Randomization will be done during surgery if the total resection of tumour will be reached and will use a stratification procedure based on center

Read the detailed description

This is a phase III randomized, multicenter study with two different arm:

  • experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin
  • comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility.

Patient will be randomized in a 1:1 ratio. Randomization will be done during surgery if the total resection of tumour will be reached and will use a stratification procedure based on center

The HIPEC CO2 regimen will be as reported below:

mitomycin: (total dose of 35 mg/mq, physiologic solution 0.9%) administrated 50% at time 0 from start of HIPEC CO2 treatment (17.5 mg/mq), 25% (8.8 mg/mq) after 30 minutes and the last dose 25% after 60 minutes. Recommended temperature for HIPEC treatment is 41-42 °C for 90 minutes.

Adjuvant treatment consists of a 6 months chemotherapy after surgery. It is possible to choose between Oxaliplatin, Capecitabine (XELOX) or Oxaliplatin, Fluorouracil, Leucovorin (FOLFOX-4) Patients affected by CRC at high risk of developing peritoneal carcinomatosis will be randomized in the study.

02

Conditions studied

  • Colorectal Neoplasms

Keywords

  • colorectal cancer
  • HIPEC CO2
  • prophylactic surgery
  • mitomycin
03

In context

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's planned enrollment of 330 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Browse Colorectal Neoplasms studies →

Lead sponsor

Mario Negri Institute for Pharmacological Research is the lead sponsor of 159 studies on the registry; 36 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients with histologically documented colorectal adenocarcinoma eligible for R0,

    1. Presurgical or intraoperative stage T4a or T4b primary tumour (TNM 8 th)
    2. Urgent presentation: perforation without purulent generalized peritonitis or fecal peritonitis
    3. Peritumoral minimal peritoneal carcinomatosis: limited peritoneal disease in close proximity to the primary tumour, that may be removed en bloc
    4. Ovarian metastases (Krukenberg tumor)
  2. Age ≥ 18 and ≤75 years
  3. Written informed consent

Exclusion criteria

Exclusion Criteria:

  1. Distant metastatic disease (even if limited and completely resected)
  2. History of tumour diagnosed in the 3 years before entering the study, except for topical and healed pathologies that do not need further treatment (e.g. non-melanoma skin carcinomas, superficial bladder carcinomas or in situ carcinoma of the breast or cervix).
  3. Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
  4. Poor general conditions (ECOG > 2).
  5. Impaired cardiac function (history of congestive heart failure or FE \<40%). Clinically significant cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrolment), myocardial infarction (\<6 months prior to enrolment), unstable angina, congestive heart failure (New York Heart Association Classification Class > II or serious uncontrolled cardiac Arythmia requiring medication
  6. Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance \<60 mL / min)
  7. Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin> 1.5 upper limit of normal)
  8. Impaired hematopoietic function (leucocytes \<4000 / mm3, neutrophils \<1500 / mm3, platelets \<100000 / mm3)
  9. Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 \<50% or DLCO \<40% of normal age value).
  10. Pregnancy
  11. History or presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of HIPEC or chemotherapy or patient at high risk from treatment complications.
  12. Chronic inflammatory bowel disease
  13. Patients with acute bowel obstruction
  14. Refusal to join the study
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
330 participants (estimated)

Study arms

  • Experimental
    Experimental

    ARM A: Prophylactic surgery plus HIPEC CO2 performed with mitomycin

    Procedure: HIPEC CO2 surgery · Drug: Mitomycin

  • Active comparator
    Comparator

    ARM B: Standard surgey without HIPEC CO2 The arm B is with standard surgery without HIPEC CO2

    Procedure: Standard surgery

Interventions

  • ProcedureHIPEC CO2 surgery

    Prophylactic surgery plus HIPEC CO2 performed with mitomycin

  • ProcedureStandard surgery

    Standard surgery without HIPEC CO2

  • DrugMitomycin

    Prophylactic surgery plus HIPEC CO2 performed with mitomycin

    Also known as: HIPEC CO2 surgery with mitomycin

06

What researchers measure

Primary outcomes

  1. Local recurrence free survival (LRFS)

    The primary efficacy endpoint is LRFS defined as the time from randomization to the date of first local relapse, peritoneal carcinomatosis or death for any cause, whichever comes first.

    Time frame: This outcome measure will be assess approximately 3 years after the last patient enrolled

Secondary outcomes

  1. Disease Free Survival (DFS)

    Disease Free Survival (DFS) DFS is defined as the time from randomization to the date of first local relapse, distant relapse, peritoneal carcinomatosis or death for any cause, whichever comes first. OS is defined as the time from randomization to death for any cause.

    Time frame: This outcome measure will be assess approximately 3 years after the last patient enrolled

  2. Overall Survival (OS)

    death for any cause

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  3. number of post-surgery complication

    any type of complication

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  4. morbidity

    evaluated during and after surgery, graded according to the NCI-CTAE version 4.03 for AE related to chemotherapy and according to Clavien Dindo for surgery complications

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  5. duration of surgery

    timing of surgery

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  6. number of patients performing the adjuvant chemotherapy.

    patients performing the adjuvant chemotherapy

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  7. length of hospitalization

    length of hospitalization

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

  8. mortality at 30 and 90 days from surgery

    mortality at 30 and 90 days from surgery

    Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled

07

Study locations

12 of 16 sites recruiting
  • IRCCS Istituto Tumori Giovanni Paolo II
    Bari, Italy
    • Michele Simone · Contact
    Recruiting
  • ASP PO Sant'Elia
    Caltanissetta, Italy
    • Giovanni Ciaccio · Contact
    Recruiting
  • AO Santa Croce e Carle
    Cuneo, Italy
    Active, not recruiting
  • ULLS1 1 Dolomiti - Ospedale di Feltre
    Feltre, Italy
    Active, not recruiting
  • Ospedale dell Angelo
    Mestre, Italy
    • Maurizio Rizzo · Contact
    Recruiting
  • ASST Grande Ospedale Metropolitano Niguarda
    Milano, Italy
    • Giovanni Ferrari, MD · Contact
    Recruiting
  • Policlinico di Milano
    Milano, Italy
    • Luigi Boni · Contact
    Recruiting
  • A.O.R.N. A. Cardarelli
    Napoli, Italy
    • Carmine Antropoli · Contact
    Recruiting
  • Azienda Ospedaliera Universitaria Federico II
    Napoli, Italy
    • Francesco Corcione · Contact
    Recruiting
  • Ospedale Evangelico Betania
    Napoli, Italy
    Active, not recruiting
  • AOU Policlinico Paolo Giaccone
    Palermo, Italy
    • Antonino Agrusa · Contact
    Recruiting
  • Azienda Ospedaliera S. Camillo Forlanini
    Roma, Italy
    Active, not recruiting
  • Fondazione Policlinico Universitario A. Gemelli
    Roma, Italy
    • Roberto Persiani · Contact
    Recruiting
  • Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
    Roma, Italy
    • Fabio Pacelli, MD · Contact
    Recruiting
  • IRCCS Policlinico San Donato
    San Donato Milanese, Italy
    • Luigi Bonavina · Contact
    Recruiting
  • IRCCS Casa Sollievo della Sofferenza
    San Giovanni Rotondo, Italy
    • Francesca Bazzocchi · Contact
    Recruiting
08

References and documents

Publications

  • Pacelli F, Gerardi C, Rulli E, Abatini C, Rotolo S, Garattini S, Melotti G, Torri V, Galli F, Rulli E, Di Giorgio A; CHECK Investigators. Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in colorectal carcinoma at high risk of peritoneal carcinomatosis: short-term and long-term outcomes from the CHECK study - protocol for a randomised, multicentre, phase 3 trial. BMJ Open. 2022 Aug 1;12(8):e051324. doi: 10.1136/bmjopen-2021-051324. PubMed 35914916 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 27, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03914820
Lead sponsor
Mario Negri Institute for Pharmacological Research
Responsible party
Sponsor
First posted
Apr 16, 2019
Start date
Jun 19, 2020
Primary completion
Jun 1, 2025 (estimated)
Completion
Jun 1, 2025 (estimated)
Last update
Oct 27, 2023

Study contacts

Fabio Pacelli, MD
Contact
fabio.pacelli@policlinicogemelli.it
0039063015 ext. 7255
Chiara Gerardi
Contact
chiara.gerardi@marionegri.it
0039023901 ext. 4659
Fabio Pacelli, MD
principal investigator · fabio.pacelli@policlinicogemelli.it

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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