Colorectal Neoplasms
Conditions
Keywords
colorectal cancer, HIPEC CO2, prophylactic surgery, mitomycin
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.
Interventions
PROCEDUREHIPEC CO2 surgery
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
PROCEDUREStandard surgery
Standard surgery without HIPEC CO2
DRUGMitomycin
Prophylactic surgery plus HIPEC CO2 performed with mitomycin
Sponsors
Mario Negri Institute for Pharmacological Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 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 |
| 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 |
| 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 patients performing the adjuvant chemotherapy. | This outcome measure will be assessed approximately 3 years after the last patient enrolled | patients performing the adjuvant chemotherapy |
| length of hospitalization | This outcome measure will be assessed approximately 3 years after the last patient enrolled | length of hospitalization |
| 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 |
| duration of surgery | This outcome measure will be assessed approximately 3 years after the last patient enrolled | timing of surgery |
Countries
Italy
Contacts
Primary ContactFabio Pacelli, MD
Backup ContactChiara Gerardi
Outcome results
None listed