Adjuvant PIPAC in Gastric Cancer Patients (PIPAC-OPC4)

October 5, 2022 updated by: Michael Bau Mortensen

Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) During Laparoscopic Resection in High-risk Gastric Cancer Patients: A Multicentre Phase-I Study (the PIPAC-OPC4 Study)

In this study patients will be offered intraperitoneal atomized chemotherapy as a supplement to the standard treatment of high-risk gastric cancer (laparoscopic removal of the stomach). Two commercially available oncologic drugs will be used (doxorubicin and cisplatin).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Gastric adenocarcinoma (GAC) is considered the fifth most common cancer in the word and the third leading cause of cancer death globally. The majority of GAC patients presents with advanced stages of disease leading to a dismal prognosis even after treatments with curative intent.

Irrespective of these tumors' origin, the peritoneum is one of the most frequent sites of metastases and recurrences that generally determines the subsequent prognosis. Additionally, it is observed that none of the currently available perioperative chemotherapy regimens have been able to reduce the risk for peritoneal deposits. Peritoneal metastases (PMs) are formed during processes that entraps the malignant cells and this restrictive milieu is thought to hinder the penetrance of drugs delivered systemically and provides grounds for the early administration of intraperitoneal treatments. The presence of malignant intraperitoneal cells that is not cleared by chemotherapy before surgery, and/or seeding of malignant cells during surgery, are probably the major reasons for the development of PM and thus the poor prognosis after seemingly micro-radical surgery.

Since only a fraction of the systemically administered chemotherapy reaches the peritoneum, the effect of intraperitoneal chemotherapy has been eagerly studied. A recent systematic review and meta-analysis identified three trials evaluating the effect of intraperitoneal chemotherapy and/or extensive peritoneal lavage in gastric cancer patients who underwent subsequent surgery. Two and five-year overall survival increased significantly in patients who had intraperitoneal chemotherapy (RR=1.62 and 3.10) and survival further increased by the addition of extensive lavage (RR= 2.33 and 6.19).

The intraperitoneal delivery and subsequent uptake of chemotherapy is improved by a new aerosol technique. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has shown promising results in patients with PM from colorectal, ovarian and gastric cancer (see below), and PIPAC is feasible, safe and well tolerated by the majority of patients. Our own database assessed the outcome of PIPAC, with low-dose cisplatin and doxorubicin, in GAC patients with chemotherapy-resistant PM. Objective tumor response was documented in 40% of the patients after PIPAC, including complete histological regression in some, whereas an additional 20% had no further tumor progression (manuscript in preparation). These observations in GAC patients deliver further evidence suggesting that PIPAC can induce regression of resistant PMs in several cancer types and might meet the clinical need for new and better therapies for fatal cancer disease states. Our results also provide evidence that low-dose PIPAC therapy might be effective in treating patients with recurrent, chemo-resistant gastric PMs, including the aggressive signet-ring histology.

The imminent question is whether PIPAC delivered immediately after a laparoscopic gastrectomy for GAC, in patients being exposed to a significant risk of early recurrent disease, can be safely carried out? If so, for the first time, a corresponding therapeutic concept can be offered to similar GAC patients in addition to surgery with curative intent. This could potentially increase progression free and eventually overall survival.

Twenty patients will be enrolled from two Danish and Swedish hospitals according to the inclusion and exclusion criteria and included in the data analysis if laparoscopic removal of the stomach and subsequent immediate PIPAC has been performed.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Odense, Denmark, 5000
        • Odense PIPAC Center, Department of Surgery, Odense University Hospital
  • Sweden
      • Stockholm, Sweden
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with high-risk GAC defined as: Diffuse cancer (signet ring cells predominant) or clinical stage: cTany + cN2-3 or cT3-T4 + cNany or GAC patients with preoperative positive peritoneal cytology submitted to laparoscopic gastrectomy (+/- neoadjuvant treatment).
  • Age 18 or above
  • Written informed consent
  • Women must be postmenopausal or use adequate contraception with a negative pregnancy test at inclusion.

Exclusion Criteria:

  • Previous allergic reaction to cisplatin, doxorubicin or other platinum containing compounds.
  • Renal impairment, defined as GFR < 40 ml/min (Cockcroft-Gault Equation).
  • Myocardial insufficiency, defined as NYHA class 3-4.
  • Impaired liver function defined as bilirubin ≥ 1.5 x UNL (upper normal limit).
  • Inadequate haematological function defined as absolute neutrophil count (ANC) ≤ 1.5 x 10^9/l and platelets ≤ 100 x 10^9/l.
  • Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High-risk gastric cancer patients
The study population of high-risk gastric cancer patients will be offered one session of PIPAC immediately after laparoscopic removal of the stomach.
Drug: Doxorubicin
Conventional PIPAC with doxorubicin (2.1 mg/m2 body surface in 50ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.
Drug: Cisplatin
Conventional PIPAC with cisplatin (10.5 mg/m2 body surface in 150ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medical adverse events
Time Frame: 30 days
According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
30 days
Surgical complications
Time Frame: 30 days
According to the Dindo-Clavien classification
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay
Time Frame: 30 days
The amount of time the patient is hospitalized
30 days
Positive peritoneal lavage
Time Frame: 30 days
The rate of positive peritoneal lavage before and after surgery
30 days
Adjuvant chemotherapy
Time Frame: 30 days
The number of patients that receive adjuvant systemic chemotherapy
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michael Bau Mortensen

Investigators

  • Principal Investigator: Signe Bremholm Ellebæk, MD, PhD, Odense University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2020

Primary Completion (Actual)

June 30, 2022

Study Completion (Actual)

October 1, 2022

Study Registration Dates

First Submitted

August 2, 2019

First Submitted That Met QC Criteria

August 4, 2019

First Posted (Actual)

August 6, 2019

Study Record Updates

Last Update Posted (Actual)

October 6, 2022

Last Update Submitted That Met QC Criteria

October 5, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIPAC-OPC4

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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