Clinical trial NCT03914820: Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Colorectal Carcinoma. CHECK 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Neoplasms
Keywords: colorectal cancer
HIPEC CO2
prophylactic surgery
mitomycin
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:

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

Primary outcomes:
measure: Local recurrence free survival (LRFS)
timeFrame: This outcome measure will be assess approximately 3 years after the last patient enrolled
Secondary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: This outcome measure will be assess approximately 3 years after the last patient enrolled
measure: Overall Survival (OS)
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: number of post-surgery complication
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: morbidity
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: duration of surgery
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: number of patients performing the adjuvant chemotherapy.
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: length of hospitalization
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: mortality at 30 and 90 days from surgery
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
Other outcomes:
Locations:
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
city: Caltanissetta
country: Italy
facility: ASP PO Sant'Elia
city: Cuneo
country: Italy
facility: AO Santa Croce e Carle
city: Feltre
country: Italy
facility: ULLS1 1 Dolomiti - Ospedale di Feltre
city: Mestre
country: Italy
facility: Ospedale dell Angelo
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Milano
country: Italy
facility: Policlinico di Milano
city: Napoli
country: Italy
facility: A.O.R.N. A. Cardarelli
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Napoli
country: Italy
facility: Ospedale Evangelico Betania
city: Palermo
country: Italy
facility: AOU Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Camillo Forlanini
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
Study officials:
affiliation: fabio.pacelli@policlinicogemelli.it
name: Fabio Pacelli, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.