Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC)

Not Applicable

Recruiting

• Conditions: Peritoneal Metastases From Colorectal Cancer
• Interventions: Procedure: Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

• Registration Number: NCT06091683
• Lead Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-04-30
• Status Verified: 2023-10
• Study First Submitted: 2023-10-16
• Study First Submitted QC: 2023-10-16
• Last Update Submitted: 2023-10-16
• Study First Posted: 2023-10-19
• Last Update Posted: 2023-10-19
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Histopathological diagnosis of intestinal type, mucinous or signet ring cell adenocarcinoma of the colon (with upper limit of the tumor above peritoneal reflection);

2. curative (microscopically complete) surgery performed by laparotomy or laparoscopy;

3. 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);

4. age > 18;

5. performance status 2 according to the World Health Organization score;

6. willingness to start adjuvant systemic chemotherapy and post-operative follow-up;

7. Signing of informed consent.

Exclusion Criteria

1. active sepsis;
2. cardiac function impairment (history of previous heart failure or 40% ejection fraction);
3. renal impairment (serum creatinine >1.5 normal value or creatinine clearance 60 ml/min);
4. liver function impairment (aspartate aminotransferase, alanine aminotransferase, bilirubin > 1.5 normal value);
5. bone marrow function impairment (leukocytes 4000 / mm3, neutrophils 1500 /mm3, platelets 80000/mm3);
6. 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);
7. extra-abdominal and/or hepatic metastases at the Computed Tomography scan of the chest, abdomen and pelvis with intravenous contrast;
8. severe complications (grade 3-4) after primary cancer surgery;
9. haemorrhagic diathesis or coagulopathy;
10. pregnancy or lactation in progress;
11. 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..

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)	Pressurized intraperitoneal aerosol chemotherapy (PIPAC)	Preliminary laparoscopic exploration of the abdominal cavity and adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin and concurrent intravenous infusion of 5-fluorouracil and folinic acid.

Primary Outcome Measures

Name	Time	Method
Feasibility of adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)	12 weeks	The adjuvant PIPAC performed in an early setting after primary surgery will be considered feasible if: * the laparoscopic procedure can be completed in 9 patients; * the postoperative stay will be three days or shorter in ≥6 patients; * the post-operative adjuvant s-CT will begin within 12 weeks of primary surgery in ≥ 9 patients.
Safety of adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)	30 days	The adjuvant PIPAC will be considered a well tolerated procedure if: * a maximum of one serious treatment-related complication will occur; * a maximum of one laparotomy conversion will occur; * a maximum of one hospital readmission will occur within 30 days.

Secondary Outcome Measures

Name	Time	Method
Peritoneal disease-free survival	60 months	Peritoneal disease-free survival will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis,
Overall survival	60 months	Overall survival will be measured from the date of primary surgery to the date of death for any cause or, for patients still alive at the date of the last available follow-up.
Disease-free survival	60 months	Disease-free survival will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis, systemic metastases or death.

Trial Locations

Locations (1)

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy