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

Pilot Study of Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for the Prevention of Peritoneal Metastases After Curative-intent Surgery for High-risk Colorectal Cancer.

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.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Metastases From Colorectal Cancer
• Intervention / Treatment: Procedure: Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dario Baratti, MD; Phone Number: 3441 +390223901; Email: dario.baratti@istitutotumori.mi.it

Study Locations

• Italy
  • Milano, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Contact: Dario Baratti, MD; Phone Number: +390223903441; Email: dario.baratti@istitutotumori.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adjuvant 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.

Procedure: Pressurized intraperitoneal aerosol chemotherapy (PIPAC); Laparoscopic exploration of the abdominal cavity with dissection of adhesions and biopsies of suspect findings (if needed). PIPAC will be administered with oxaliplatin (92 mg/m2 body surface area in 150 ml dextrose solution) for 30 minutes under the following spraying conditions: cytostatic application at a rate of 30 ml/min, pressure of 1380 kilo-pascal over 30 minutes, and temperature of 22°C. One hour before the beginning of PIPAC, intravenous infusion of 5-fluorouracil (400 mg/m2) and folinic acid (20mg/m2) will be initiated. Standard protectionist procedures will be adopted to avoid contamination of operators and the environment with nebulized chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)	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.	12 weeks
Safety of adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)	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.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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.	60 months
Disease-free survival	Disease-free survival will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis, systemic metastases or death.	60 months
Peritoneal disease-free survival	Peritoneal disease-free survival will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis,	60 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Dario Baratti, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: INT 0068/20; 2020-000604-11 (EudraCT Number); BRI D/17/1DB (Other Grant/Funding Number: Fondazione IRCCS Istituto Nazionale Tumori. Milano (Italy)); SC 2020-000604-11_ID_18605 (Other Identifier: Agenzia Italiana del Farmaco (AIFA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: I confirm that we have a plan to make individual participant data (IPD) available to other researchers through publicly available database
• IPD Sharing Time Frame: after the completion of the study, for additional 60 months
• IPD Sharing Access Criteria: upon reasonable request to the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No