PIPAC-OPC4: Adjuvant PIPAC in Gastric Cancer Patients

Sponsor

Michael Bau Mortensen (Other)

Overall Status

Recruiting

CT.gov ID

NCT04047004

Collaborator

(none)

Enrollment

Locations

Arm

21.7

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma Gastric Cancer	Drug: Doxorubicin Drug: Cisplatin	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective, multicenter, non-randomized, non-blinded, open-labelProspective, multicenter, non-randomized, non-blinded, open-label

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Mar 11, 2020

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Medical adverse events [30 days]
According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Surgical complications [30 days]
According to the Dindo-Clavien classification

Secondary Outcome Measures

Length of stay [30 days]
The amount of time the patient is hospitalized
Positive peritoneal lavage [30 days]
The rate of positive peritoneal lavage before and after surgery
Adjuvant chemotherapy [30 days]
The number of patients that receive adjuvant systemic chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.