PIPAC for Peritoneal Metastases

Study Overview
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Brief Summary
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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system that allows the direct application of chemotherapeutic agents into the peritoneal cavity. It boosts improved distribution, enhanced tissue uptake and repeatability using minimally invasive access. It was devised to palliate the local symptoms of extensive peritoneal metastases (PM) in patients who are not amenable to curative surgery. This study is to determine safety and feasibility of PIPAC in patients with PM from Gastrointestinal (GI) cancer, Hepato-Pancreato-Biliary (HPB) cancer, and other rare malignancies.

Official Title
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Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases

Conditions
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Peritoneal Metastases

Intervention / Treatment
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* Combination Product: PIPAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Unesectable PM Group: Age ≥ 21 years old ECOG < 3 Fit for systemic chemotherapy treatment Adequate bone marrow function (haemoglobin ≥ 8.0 mmol/L, neutrophils ≥ 1.5X109/L, platelets ≥ 100X109/L Adequate renal function (e-GFR > 30mls/min for patients undergoing PIPAC with oxaliplatin; e-GFR > 60mls/min for patients undergoing PIPAC with Doxorubicine/Cisplatin) Adequate liver function (Total bilirubin < 1.5 upper limit of normal; ALT and AST< 3 upper limit of normal) No contraindications to chemotherapy agents oxaliplatin, doxorubicin/ cisplatin No contraindications to general anaesthesia and diagnostic laproscopy procedure Normal left ventricular ejection fraction (for patients undergoing PIPAC with doxorubicin/ cisplatin) Histological/ cytological proof of PM from GI, HPB, Gynaecology, Breast, Sarcoma primaries Peritoneal-dominant metastatic disease For the Extensive PM Group: All the above mentioned criteria as for the unresectable group, with the addition of the following: Not suitable for curative cytoreductive surgery (CRS) & hyperthermic intraperitoneal chemotherapy (HIPEC) surgery after diagnostic laproscopy - PCI > 18 in LGI, PCI > 6 in UGI ECOG < 3 In UGI PM patients, progression while on bidirectional chemotherapy Exclusion Criteria: Patient is medically unfit for surgery due to concurrent medical comorbidities, including but not limited to intestinal obstruction, multiple sites of metastases Any medical or psychiatric condition(s) which would preclude informed consent Patient is pregnant or nursing GI PM patients with PCI >6 but are treatment naive (these patients should undergo standard treatment - bidirectional intravenous and intraperitoneal chemotherapy)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unresectable PM group<br>Patients who have progressed on conventional systemic therapy and PIPAC is used as a palliative strategy. | Combination Product: PIPAC<br>* A novel drug delivery system using the CapnoPen device which allows the aerolisation of chemotherapeutic agents within the peritoneal cavity. PIPAC procedure will be carried out with either oxaliplatin or doxorubicin/ cisplatin.<br>|
| Experimental: Extensive PM group<br>Patients who have significant volume of peritoneal disease are treated with the intent for potential conversion to curative surgery. Role of PIPAC is as an adjunct to systemic chemotherapy to downstage peritoneal metastases. | Combination Product: PIPAC<br>* A novel drug delivery system using the CapnoPen device which allows the aerolisation of chemotherapeutic agents within the peritoneal cavity. PIPAC procedure will be carried out with either oxaliplatin or doxorubicin/ cisplatin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with major toxicities of at least CTCAE Grade 3 and above | To determine and safety and feasibility of PIPAC in patients with PM. Common Terminology Criteria for Adverse Events (CTCAE) measures Grade 1 to 5, with higher grade indicating greater severity. | Up to 4 weeks after each PIPAC procedure | 
| Number of patients with minor toxicities of CTCAE Grade 1 and 2 | Common Terminology Criteria for Adverse Events (CTCAE) measures Grade 1 to 5, with higher grade indicating greater severity. | Up to 4 weeks after each PIPAC procedure | 
| Length of hospitalisation stay for each PIPAC procedure |  | Through study completion, an average of half a year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-operative Peritoneal Carcinomatosis Index (PCI) score | To examine the clinical response of PM after PIPAC. PCI score from 0 to 39 with a higher number representing a greater amount of disease present in the peritoneum. | During each PIPAC procedure | 
| Ascites volume | To examine the clinical response of PM after PIPAC | During each PIPAC procedure | 
| Peritoneal Regression Grading Score (PRGS) from PM biopsy | To examine the clinical response of PM after PIPAC | At each PIPAC procedure | 
| Quality of Life Assessment using Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire | Range: 0-108. A high score represents a better health state | At 4 time points - Baseline (before any PIPAC procedure), pre-2nd PIPAC (Before 2nd PIPAC procedure), pre-3rd PIPAC (before 3rd PIPAC procedure) and 4 weeks post-3rd PIPAC (4 weeks after 3rd PIPAC procedure) | 
| Quality of Life Assessment using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Quality of life questionnaire | Range: 0-100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems. | At 4 time points - Baseline (before any PIPAC procedure), pre-2nd PIPAC (Before 2nd PIPAC procedure), pre-3rd PIPAC (before 3rd PIPAC procedure) and 4 weeks post-3rd PIPAC (4 weeks after 3rd PIPAC procedure) | 
| Progression free survival |  | From the start of the first PIPAC procedure, up to 5 years | 
| Overall survival |  | From the start of the first PIPAC procedure, up to 5 years | 
| Percentage of patients that convert to curative surgery | (Only applicable for Extensive PM group) | From the start of the first PIPAC procedure, up to 24 weeks ± 4 weeks |