Colorectal NeoplasmsCHECKNCT03914820
Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK Study.
A study testing HIPEC CO2 surgery, Standard surgery and Mitomycin in people with Colorectal Neoplasms, run by Mario Negri Institute for Pharmacological Research at 16 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- HIPEC CO2 surgery, Standard surgery and Mitomycin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 16 sitesItaly
- Study dates
- 19 Jun 2020to 1 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients with histologically documented colorectal adenocarcinoma eligible for R0,
- Presurgical or intraoperative stage T4a or T4b primary tumour (TNM 8 th)
- Urgent presentation: perforation without purulent generalized peritonitis or fecal peritonitis
- Peritumoral minimal peritoneal carcinomatosis: limited peritoneal disease in close proximity to the primary tumour, that may be removed en bloc
- Ovarian metastases (Krukenberg tumor)
- Age ≥ 18 and ≤75 years
- Written informed consent
Who cannot join
- Distant metastatic disease (even if limited and completely resected)
- 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).
- Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
- Poor general conditions (ECOG > 2).
- 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
- Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance <60 mL / min)
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- Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin> 1.5 upper limit of normal)
- Impaired hematopoietic function (leucocytes <4000 / mm3, neutrophils <1500 / mm3, platelets <100000 / mm3)
- Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 <50% or DLCO <40% of normal age value).
- Pregnancy
- 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.
- Chronic inflammatory bowel disease
- Patients with acute bowel obstruction
- Refusal to join the study
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites, 12 recruiting
- Recruiting
IRCCS Istituto Tumori Giovanni Paolo II
Bari
Michele Simone
- Recruiting
ASP PO Sant'Elia
Caltanissetta
Giovanni Ciaccio
- Active, not recruiting
AO Santa Croce e Carle
Cuneo
- Active, not recruiting
ULLS1 1 Dolomiti - Ospedale di Feltre
Feltre
- Recruiting
Ospedale dell Angelo
Mestre
Maurizio Rizzo
- Recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milan
Giovanni Ferrari, MD
- Recruiting
Policlinico di Milano
Milan
Luigi Boni
- Recruiting
A.O.R.N. A. Cardarelli
Naples
Carmine Antropoli
- Recruiting
Azienda Ospedaliera Universitaria Federico II
Naples
Francesco Corcione
- Active, not recruiting
Ospedale Evangelico Betania
Naples
- Recruiting
AOU Policlinico Paolo Giaccone
Palermo
Antonino Agrusa
- Active, not recruiting
Azienda Ospedaliera S. Camillo Forlanini
Roma
- Recruiting
Fondazione Policlinico Universitario A. Gemelli
Roma
Roberto Persiani
- Recruiting
Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
Roma
Fabio Pacelli, MD
- Recruiting
IRCCS Policlinico San Donato
San Donato Milanese
Luigi Bonavina
- Recruiting
IRCCS Casa Sollievo della Sofferenza
San Giovanni Rotondo
Francesca Bazzocchi
About this study
Official title: Prophylactic Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC CO2) Versus Standard Surgery in Colorectal Carcinoma at High Risk Peritoneal Carcinomatosis. Short and Long-term Outcomes. CHECK STUDY
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.
- Conditions
- Colorectal Neoplasms
- Being tested
- HIPEC CO2 surgery, Standard surgery, Mitomycin
- Keywords
- colorectal cancer, HIPEC CO2, prophylactic surgery, mitomycin
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIPEC CO2 surgeryProcedure or surgery
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Standard surgeryProcedure or surgery
Standard surgery without HIPEC CO2
MitomycinDrug
Also called HIPEC CO2 surgery with mitomycin
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | ARM A: Prophylactic surgery plus HIPEC CO2 performed with mitomycin Receives: Procedure: HIPEC CO2 surgery; Drug: Mitomycin |
| Comparator | Active comparator | ARM B: Standard surgey without HIPEC CO2 The arm B is with standard surgery without HIPEC CO2 Receives: Procedure: Standard surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: This outcome measure will be assess approximately 3 years after the last patient enrolled
Secondary outcomes (8)
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.
Measured: This outcome measure will be assess approximately 3 years after the last patient enrolled
Overall Survival (OS)
death for any cause
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
number of post-surgery complication
any type of complication
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
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
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
duration of surgery
timing of surgery
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
number of patients performing the adjuvant chemotherapy.
patients performing the adjuvant chemotherapy
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
length of hospitalization
length of hospitalization
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
mortality at 30 and 90 days from surgery
mortality at 30 and 90 days from surgery
Measured: This outcome measure will be assessed approximately 3 years after the last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2019
- Study start19 Jun 2020
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model 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
- Masking
- None (open label)
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fabio Pacelli, MD, Principal investigator, fabio.pacelli@policlinicogemelli.it
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03914820
- Sponsor's protocol ID
- IRFMN-CRC- 7813
- Other IDs
- 2019-001437-14, 2019
- Acronym
- CHECK
- Status last verified
- Oct 2023
- First submitted
- 2 Apr 2019
- Last updated
- 27 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylactic Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC CO2) Versus Standard Surgery in Colorectal Carcinoma at High Risk Peritoneal Carcinomatosis. Short and Long-term Outcomes. CHECK STUDY
- ClinicalTrials.gov ID
- NCT03914820
- Acronym / sponsor ID
- CHECK / IRFMN-CRC- 7813
- Conditions
- Colorectal Neoplasms
- Keywords
- colorectal cancer, HIPEC CO2, prophylactic surgery, mitomycin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 19 Jun 2020 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 16 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model 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
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Procedure: HIPEC CO2 surgery, Drug: MitomycinARM A: Prophylactic surgery plus HIPEC CO2 performed with mitomycin |
| Comparator | Active comparator | Procedure: Standard surgeryARM B: Standard surgey without HIPEC CO2 The arm B is with standard surgery without HIPEC CO2 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with histologically documented colorectal adenocarcinoma eligible for R0,
- Age ≥ 18 and ≤75 years
- Written informed consent
Key exclusion criteria (14 listed)
- Distant metastatic disease (even if limited and completely resected)
- 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).
- Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
- Poor general conditions (ECOG > 2).
- 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
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 |
|---|---|---|
| HIPEC CO2 surgeryProphylactic surgery plus HIPEC CO2 performed with mitomycin | Procedure or surgery | Experimental |
| Standard surgeryStandard surgery without HIPEC CO2 | Procedure or surgery | Comparator |
| MitomycinAlso: HIPEC CO2 surgery with mitomycinProphylactic surgery plus HIPEC CO2 performed with mitomycin | Drug | Experimental |
Primary outcome
Local recurrence free survival (LRFS)
Time frame: This outcome measure will be assess approximately 3 years after the last patient enrolled
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.
8 secondary outcomes
Disease Free Survival (DFS)
Time frame: This outcome measure will be assess approximately 3 years after the last patient enrolled
Overall Survival (OS)
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
number of post-surgery complication
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
morbidity
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
duration of surgery
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
number of patients performing the adjuvant chemotherapy.
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
length of hospitalization
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
mortality at 30 and 90 days from surgery
Time frame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2023.
- Derived from this study: PubMed 35914916Pacelli 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.
- Individual participant dataSharing planned: No
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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.
Fabio Pacelli, MD principal investigator
fabio.pacelli@policlinicogemelli.it
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HIPEC CO2 surgery, Standard surgery and Mitomycin in people with Colorectal Neoplasms, run by Mario Negri Institute for Pharmacological Research at 16 sites in Italy.
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: status not confirmed, as of the sponsor's last update on 27 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabio Pacelli, MD (0039063015 ext. 7255, fabio.pacelli@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local recurrence free survival (LRFS) (time frame: This outcome measure will be assess approximately 3 years after the last patient enrolled). 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 NCT03914820, which also lists 1 linked publication.
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 27 Oct 2023; AzTrials last refreshed its copy on 1 Nov 2026.