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

Colorectal Neoplasms Clinical Trial

— 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. CHECK STUDY

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03914820
• Other study ID #: IRFMN-CRC- 7813
• Secondary ID: 2019-001437-14
• Status: Recruiting
• Phase: N/A
• Start date: June 19, 2020
• Est. completion date: June 1, 2025

Study information

• Verified date: October 2023
• Source: Mario Negri Institute for Pharmacological Research
• Contact: Fabio Pacelli, MD
• Phone: 0039063015
• Email: fabio.pacelli[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. Randomization will be done during surgery if the total resection of tumour will be reached and will use a stratification procedure based on center

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 330
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Procedure:
• HIPEC CO2 surgery
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
• Standard surgery
Standard surgery without HIPEC CO2

Drug:
• Mitomycin
Prophylactic surgery plus HIPEC CO2 performed with mitomycin

Locations

Country	Name	City	State
Italy	IRCCS Istituto Tumori Giovanni Paolo II	Bari
Italy	ASP PO Sant'Elia	Caltanissetta
Italy	AO Santa Croce e Carle	Cuneo
Italy	ULLS1 1 Dolomiti - Ospedale di Feltre	Feltre
Italy	Ospedale dell Angelo	Mestre
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Policlinico di Milano	Milano
Italy	A.O.R.N. A. Cardarelli	Napoli
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Ospedale Evangelico Betania	Napoli
Italy	AOU Policlinico Paolo Giaccone	Palermo
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	IRCCS Policlinico San Donato	San Donato Milanese
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	This outcome measure will be assess approximately 3 years after the last patient enrolled
Secondary	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.	This outcome measure will be assess approximately 3 years after the last patient enrolled
Secondary	Overall Survival (OS)	death for any cause	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	number of post-surgery complication	any type of complication	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	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	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	duration of surgery	timing of surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	number of patients performing the adjuvant chemotherapy.	patients performing the adjuvant chemotherapy	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	length of hospitalization	length of hospitalization	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	mortality at 30 and 90 days from surgery	mortality at 30 and 90 days from surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled