Back to resultsProphylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK Study. (CHECK)
Primary Purpose
Colorectal Neoplasms
Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
HIPEC CO2
Standard surgery
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring colorectal cancer, HIPEC CO2, prophylactic surgery , mitomycin
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- 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)
- 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
Sites / Locations
- IRCCS Istituto Tumori Giovanni Paolo IIRecruiting
- ASP PO Sant'EliaRecruiting
- AO Santa Croce e Carle
- ULLS1 1 Dolomiti - Ospedale di Feltre
- Ospedale dell Angelo
- ASST Grande Ospedale Metropolitano NiguardaRecruiting
- Policlinico di Milano
- A.O.R.N. A. Cardarelli
- Azienda Ospedaliera Universitaria Federico II
- Ospedale Evangelico Betania
- AOU Policlinico Paolo Giaccone
- Azienda Ospedaliera S. Camillo Forlanini
- Fondazione Policlinico Universitario A. Gemelli
- Fondazione Policlinico Universitario A. GemelliRecruiting
- Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro CuoreRecruiting
- IRCCS Policlinico San Donato
- IRCCS Casa Sollievo della Sofferenza
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental
Comparator
Arm Description
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Standard surgey without HIPEC CO2
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Overall Survival (OS)
death for any cause
number of post-surgery complication
any type of complication
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
duration of surgery
timing of surgery
number of patients performing the adjuvant chemotherapy.
patients performing the adjuvant chemotherapy
length of hospitalization
length of hospitalization
mortality at 30 and 90 days from surgery
mortality at 30 and 90 days from surgery
Full Information
NCT ID
NCT03914820
First Posted
April 2, 2019
Last Updated
June 16, 2021
Sponsor
Mario Negri Institute for Pharmacological Research
1. Study Identification
Unique Protocol Identification Number
NCT03914820
Brief Title
Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK Study.
Acronym
CHECK
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. A Collaborative Randomized Controlled Trial of: ACOI, FONDAZIONE AIOM, SIC, SICE, SICO. CHECK STUDY
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2020 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mario Negri Institute for Pharmacological Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
Keywords
colorectal cancer, HIPEC CO2, prophylactic surgery , mitomycin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
330 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Arm Title
Comparator
Arm Type
Active Comparator
Arm Description
Standard surgey without HIPEC CO2
Intervention Type
Procedure
Intervention Name(s)
HIPEC CO2
Intervention Description
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Intervention Type
Procedure
Intervention Name(s)
Standard surgery
Intervention Description
Standard surgery without HIPEC CO2
Primary Outcome Measure Information:
Title
Local recurrence free survival (LRFS)
Description
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 Outcome Measure Information:
Title
Disease Free Survival (DFS)
Description
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
Title
Overall Survival (OS)
Description
death for any cause
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
Title
number of post-surgery complication
Description
any type of complication
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
Title
morbidity
Description
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
Title
duration of surgery
Description
timing of surgery
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
Title
number of patients performing the adjuvant chemotherapy.
Description
patients performing the adjuvant chemotherapy
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
Title
length of hospitalization
Description
length of hospitalization
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
Title
mortality at 30 and 90 days from surgery
Description
mortality at 30 and 90 days from surgery
Time Frame
This outcome measure will be assessed approximately 3 years after the last patient enrolled
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabio Pacelli, MD
Phone
0039063015
Ext
7255
Email
fabio.pacelli@policlinicogemelli.it
First Name & Middle Initial & Last Name or Official Title & Degree
Erica Rulli
Phone
0039023901
Ext
4684
Email
erica.rulli@marionegri.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabio Pacelli, MD
Organizational Affiliation
fabio.pacelli@policlinicogemelli.it
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS Istituto Tumori Giovanni Paolo II
City
Bari
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michele Simone
Facility Name
ASP PO Sant'Elia
City
Caltanissetta
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Ciaccio
Facility Name
AO Santa Croce e Carle
City
Cuneo
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
ULLS1 1 Dolomiti - Ospedale di Feltre
City
Feltre
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Ospedale dell Angelo
City
Mestre
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
ASST Grande Ospedale Metropolitano Niguarda
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Ferrari, MD
Facility Name
Policlinico di Milano
City
Milano
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
A.O.R.N. A. Cardarelli
City
Napoli
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Ospedale Evangelico Betania
City
Napoli
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
AOU Policlinico Paolo Giaccone
City
Palermo
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Azienda Ospedaliera S. Camillo Forlanini
City
Roma
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Fondazione Policlinico Universitario A. Gemelli
City
Roma
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Fondazione Policlinico Universitario A. Gemelli
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Persiani
Facility Name
Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Pacelli, MD
Facility Name
IRCCS Policlinico San Donato
City
San Donato Milanese
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
IRCCS Casa Sollievo della Sofferenza
City
San Giovanni Rotondo
Country
Italy
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35914916
Citation
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.
Results Reference
derived
Learn more about this trial
Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK Study.
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