Second Look Laparoscopy in Colorectal Cancer (HIPEC)

• number of patients with peritoneal carcinosis diagnosed at laparoscopy in the experimental arm [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• changes in quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  quality of life is measured at baseline and 6 months after randomization
• overall survival [ Time Frame: five years ] [ Designated as safety issue: No ]
• worst grade adverse event per patient [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
  toxicity measured only in experimental arm, weekly from randomization to 30 days after experimental treatment
• number of patients with radiologic evidence of disease after initial surgery [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• list of therapies and clinical outcomes of patients who had radiologic evidence of disease within 6 months after initial surgery [ Time Frame: two years ] [ Designated as safety issue: No ]
  description of therapies and outcomes for those patients who were not randomized due to presence of disease

The purpose of this study is to evaluate whether a second-look laparoscopy, followed by peritonectomy, hyperthermic intraperitoneal chemotherapy (HIPEC) or systemic chemotherapy in case of peritoneal carcinosis, improves the overall survival of patients who have had radical resection of mucinous colorectal cancer.

Patients will be entered into the study after radical resection of mucinous colorectal cancer, and reevaluated by CT scan after 6 months. Patients with no evidence of disease will be randomized to receive either standard follow up, or to have a second look laparoscopy to evaluate for peritoneal carcinosis. After laparoscopy, those patients who do not have peritoneal carcinosis will continue with standard follow up. Patients with peritoneal carcinosis diagnosed by laparoscopy will be treated according to their peritoneal carcinosis index (PCI). For patients with PCI > 20, systemic chemotherapy will be given according to Italian Association of Medical Oncology (AIOM) guidelines. Patients with PCI < 20 will undergo peritonectomy and then receive intravenous chemotherapy immediately followed by HIPEC.

• Procedure: Laparoscopy
  second look laparoscopy to evaluate for peritoneal carcinosis
• Procedure: peritonectomy
  for patients with PCI < 20
• Drug: Folinic Acid
  20 mg/m2 IV given just before HIPEC for patients with PCI < 20
• Drug: 5-Fluorouracil
  400 mg/m2 IV given just before HIPEC in patients with PCI < 20
• Drug: Oxaliplatin
  460 mg/m2 intraperitoneal hyperthermic perfusion for patients with PCI < 20
• Drug: systemic chemotherapy
  according to national Italian (AIOM) guidelines and may include biotherapies for patients with PCI > 20

• Experimental: Second look laparoscopy
  Second look laparoscopy to evaluate for and treat peritoneal carcinosis
  Interventions:

  • Procedure: Laparoscopy
  • Procedure: peritonectomy
  • Drug: Folinic Acid
  • Drug: 5-Fluorouracil
  • Drug: Oxaliplatin
  • Drug: systemic chemotherapy
• No Intervention: standard follow up

Inclusion Criteria:

• Histologic diagnosis colorectal adenocarcinoma
• Mucinous histotype
• Stage I-III
• Radical (R0) surgical resection of primary tumor
• CT scan with contrast showing no evidence of disease recurrence 6 months after primary surgery
• Age ≥ 18 ≤ 65 years
• Performance Status ECOG ≤1
• Normal hepatic, renal and hematologic function
• Adjuvant chemotherapy permitted
• Signed informed consent

Exclusion Criteria:

• Residual disease after surgical resection of primary tumor
• Distant metastasis
• Active systemic infection
• Chronic cardiovascular illness that would contraindicate abdominal dilatation with pneumoperitoneum
• Concomitant or previous malignancy with 5 years of surgical resection of primary tumor (except for adequately treated non-melanoma skin cancer and in situ cervical cancer)
• Pregnancy or lactation
• Refusal or incapability of providing informed consent
• Impossibility of complying with study schedules and follow-up