The Application of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Surface Malignancies (PIPAC)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel minimally invasive drug delivery system for patients with peritoneal metastases (PM). It has been considered as a safe and feasible palliative treatment alternative proven by previous phase I studies. Currently available evidence on feasibility, efficacy and tolerability in Asian populations is limited. In this open-label, single-arm, monocentric clinical trial, investigators aim to evaluate the therapeutic efficacy and complications of PIPAC with oxaliplatin as an alternative on patients of unresectable colorectal cancer with PM and doxorubicin and cisplatin on patients of unresectable gastric and pancreatic cancers with PM. Alternative regimen can be considered multidisciplinary tumour board meeting. Patients will be recruited according to the inclusion criteria and treated for 3 cycles of PIPAC and concurrent systemic chemotherapy. The goal was to repeat PIPAC every 6-8 weeks for at least three procedures, and the delay of the systemic chemotherapy is 2 weeks before and after each PIPAC procedure. If PM was considered to become resectable during PIPAC, patients were discussed at the multidisciplinary tumour board for curative intent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The primary outcome is the clinical benefit rate (CBR), measured by an independent radiologist according to Response Evaluation Criteria In Solid Tumors (RECIST) and Peritoneal Cancer Index (PCI) assessed by laparoscopy and histopathological tumour response evaluated by pathologists blinded to clinical outcomes. Key secondary outcomes include the major and minor treatment-related adverse events according to the Common Terminology Criteria for Adverse Events (CTACE) up to 4 weeks after the treatment, Cytological tumour response of peritoneal lavage or ascites, treatment-related characteristics, hospital stay, progression-free survival, overall survival and readmission rate. The proposed study duration is 3 years from the start date and the estimated sample size is 51 according to centre capacity.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Metastases
• Intervention / Treatment: Drug: Pressured Intraperitoneal Aerosol Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ian WONG, Dr.; Phone Number: +852 2255 4774; Email: iyhwong@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
    • Contact: Ian WONG, Dr.; Phone Number: +852 2255 4774; Email: iyhwong@hku.hk
    • Principal Investigator: Ian WONG, Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥18 years of old;
2. WHO performance of status 0-1;
3. Histologically or cytologically proven PM of a gastric, pancreatic or colorectal carcinoma;
4. Treatment naïve patients as first-line treatment;
5. Progression on or intolerance to first-line systemic chemotherapy as second-line treatment;
6. No symptoms of gastrointestinal obstruction;
7. No contraindications for the planned systemic therapy or laparoscopy;
8. No previous PIPAC/IP/HIPEC;
9. No other concurrent malignancies or any other malignancy within 6 months prior to enrolment;
10. Able to give written informed consent.

Exclusion Criteria:

1. A history of allergic reaction to platinum containing compounds or doxorubicin;
2. Pregnant or breastfeeding;
3. Any extra-peritoneal metastases;
4. Renal impairment, defined as GFR less than 40 mL/min;
5. Impaired liver function defined as bilirubin over 1.5 × UNL;

6. Inadequate haematological function

   • Leucocyte < 3.00 × 109/L
   • Absolute neutrophil counts < 1.50 × 109/L
   • Platelet < 100 × 109/L

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: PIPAC

Drug: Pressured Intraperitoneal Aerosol Chemotherapy; PIPAC cycles will be scheduled every 6-8 weeks and 2 weeks after the last systemic chemotherapy administration. The bidirectional program for the combination of intraperitoneal and systemic chemotherapy is designed as follows: systemic chemotherapy followed by PIPAC two weeks later, followed by a one-week interval, and then systemic chemotherapy once again until three PIPAC cycles have been completed. Up to a one-week delay in returning to systemic chemotherapy after PIPAC and vice versa were considered acceptable. Systemic drug choice was based on previous chemotherapy exposure and the medical oncologists' decision. The study ends after the 3rd cycle of PIPAC.; Other Names: PIPAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR)	Clinical benefit rate (CBR) according to Response Evaluation Criteria In Solid Tumors (RECIST).	At the end of Cycle 3 (each cycle is 6 to 8 weeks)

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Ian WONG, Dr., The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Oxaliplatin; Intraperitoneal chemotherapy; Peritoneal metastases; Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Peritoneal Diseases; Digestive System Neoplasms; Neoplastic Processes; Abdominal Neoplasms; Neoplasm Metastasis; Peritoneal Neoplasms
• Other Study ID Numbers: UW 23-361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No