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

Not Applicable

Recruiting

• Conditions: Colorectal Neoplasms
• Interventions: Procedure: HIPEC CO2 surgery; Procedure: Standard surgery; Drug: Mitomycin

• Registration Number: NCT03914820
• Lead Sponsor: Mario Negri Institute for Pharmacological Research

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.

Study Timeline

• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-11
• Study First Posted: 2019-04-16
• Study Start: 2020-06-19
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-25
• Last Update Posted: 2023-10-27
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 330

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	HIPEC CO2 surgery	ARM A: Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Experimental	Mitomycin	ARM A: Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Comparator	Standard surgery	ARM B: Standard surgey without HIPEC CO2 The arm B is with standard surgery without HIPEC CO2

Primary Outcome Measures

Name	Time	Method
Local recurrence free survival (LRFS)	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	This outcome measure will be assessed approximately 3 years after the last patient enrolled	death for any cause
duration of surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled	timing of surgery
number of patients performing the adjuvant chemotherapy.	This outcome measure will be assessed approximately 3 years after the last patient enrolled	patients performing the adjuvant chemotherapy
mortality at 30 and 90 days from surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled	mortality at 30 and 90 days from surgery
Disease Free Survival (DFS)	This outcome measure will be assess approximately 3 years after the last patient enrolled	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.
number of post-surgery complication	This outcome measure will be assessed approximately 3 years after the last patient enrolled	any type of complication
length of hospitalization	This outcome measure will be assessed approximately 3 years after the last patient enrolled	length of hospitalization
morbidity	This outcome measure will be assessed approximately 3 years after the last patient enrolled	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

Trial Locations

Locations (16)

Policlinico di Milano; 🇮🇹 Milano, Italy

ASP PO Sant'Elia; 🇮🇹 Caltanissetta, Italy

AOU Policlinico Paolo Giaccone; 🇮🇹 Palermo, Italy

ULLS1 1 Dolomiti - Ospedale di Feltre; 🇮🇹 Feltre, Italy

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

A.O.R.N. A. Cardarelli; 🇮🇹 Napoli, Italy

Azienda Ospedaliera Universitaria Federico II; 🇮🇹 Napoli, Italy

Azienda Ospedaliera S. Camillo Forlanini; 🇮🇹 Roma, Italy

Fondazione Policlinico Universitario A. Gemelli; 🇮🇹 Roma, Italy

Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore; 🇮🇹 Roma, Italy

Ospedale Evangelico Betania; 🇮🇹 Napoli, Italy

IRCCS Policlinico San Donato; 🇮🇹 San Donato Milanese, Italy

IRCCS Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

IRCCS Istituto Tumori Giovanni Paolo II; 🇮🇹 Bari, Italy

Ospedale dell Angelo; 🇮🇹 Mestre, Italy

AO Santa Croce e Carle; 🇮🇹 Cuneo, Italy