Overview
The objective of this clinical trial is to demonstrate the feasibility and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for the prevention of peritoneal metastases after curative-intent surgery for high-risk colorectal cancer.
Description
This single-arm, single-center, open-label trial enrolls patients after curative-intent surgery for colon adenocarcinoma (proximal to peritoneal reflection), intestinal or mucinous histological type, associated with the following clinical-pathological risk factors for the development of peritoneal metastases: a) stage pT4a, N0-2b, M0 of the Tumor Node Metastasis classification; b) stage pT4b, N0-2b, M0; and c) primary perforated tumor (any T, any N, M0). Eligible patients who will give informed consent undergo laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC) 4 to 8 weeks after primary surgery, followed by adjuvant systemic chemotherapy according to according to current guidelines. After the procedure, patients will be followed-up to assess occurrence of adverse events,survival, peritoneal and systemic disease relapse, and quality of life.
Eligibility
Inclusion Criteria:
- Histopathological diagnosis of intestinal type, mucinous or signet ring cell adenocarcinoma of the colon (with upper limit of the tumor above peritoneal reflection);
- curative (microscopically complete) surgery performed by laparotomy or laparoscopy;
- presence of at least one of the following risk factors for the development of
metachronous peritoneal metastases:
- perforated primary tumor (any T, N0-2b, M0);
- primary tumor infiltrating the visceral peritoneum (pT4a, N0-2b, M0), or directly invading adjacent organs (pT4b, N0-2b, M0);
- age > 18;
- performance status 2 according to the World Health Organization score;
- willingness to start adjuvant systemic chemotherapy and post-operative follow-up;
- Signing of informed consent.
Exclusion Criteria:
- active sepsis;
- cardiac function impairment (history of previous heart failure or 40% ejection fraction);
- renal impairment (serum creatinine >1.5 normal value or creatinine clearance 60 ml/min);
- liver function impairment (aspartate aminotransferase, alanine aminotransferase, bilirubin > 1.5 normal value);
- bone marrow function impairment (leukocytes 4000 / mm3, neutrophils 1500 /mm3, platelets 80000/mm3);
- lung function impairment (diagnosis of severe chronic obstructive pulmonary disease or 50% forced expiratory volume at one second or 40% diffusion capacity of lung for carbon monoxide adjusted for age);
- extra-abdominal and/or hepatic metastases at the Computed Tomography scan of the chest, abdomen and pelvis with intravenous contrast;
- severe complications (grade 3-4) after primary cancer surgery;
- haemorrhagic diathesis or coagulopathy;
- pregnancy or lactation in progress;
- psychiatric or neurological conditions such as to preclude protocol procedures; 12) contraindications to laparoscopy; 13) known hypersensitivity to oxaliplatin or other platinum containing compounds and/or to any of their excipients; 14) history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma; 15) prior pre-operative radio-chemotherapy..