PIPAC With Nab-paclitaxel and Cisplatin in Peritoneal Carcinomatosis

Study Overview
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Brief Summary
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Phase Ib trial including investigating the combination of nab-paclitaxel and cisplatin in patients diagnosed with peritoneal carcinomatosis related to pancreatic, oeso-gastric, ovarian cancer or primitive peritoneal mesothelioma.

Detailed Description
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Phase Ib trial investigating the combination of intraperitoneal Cisplatin (10.5 mg/m2) and Nab-paclitaxel (escalated dose from 7.5 mg/m2 to 70 mg/m2) administered by pressurized intraperitoneal aerosol chemotherapy (PIPAC) every 4-6 weeks for 3 cycles.

Official Title
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A Phase Ib Trial of Intraperitoneal Cisplatin and Nab-paclitaxel Administered by Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Advanced Malignancies Confined to the Peritoneal Cavity

Conditions
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Peritoneal Carcinomatosis

Intervention / Treatment
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* Drug: Nab paclitaxel
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Informed consent as documented by signature ≥18 years, psychologically able to follow the trial procedures with peritoneal carcinomatosis from pancreatic, oesogastric, epithelial ovarian cancers or primitive peritoneal mesothelioma, ECOG 0, 1 or 2, Life expectancy > 3 months, Not candidate for surgical cytoreduction and IP/HIPEC based on expert multidisciplinary board who received at least one line of chemotherapy and for whom standard therapies have been exhausted or not feasible. patients with residual disease following the first line of therapy or Following secondary debulking are eligible. Exclusion criteria: Predominant extra-peritoneal metastases at the discretion of the study team after discussion at the multidisciplinary board, Bowel obstruction, active gastro-duodenal ulcer or ongoing abdominal infection (bacterial, viral or fungal), Chemotherapy or surgery within the last two weeks prior to enrollment, Previous intra-abdominal chemotherapy, General or local (abdominal) contra-indications for laparoscopic surgery Known allergy to cisplatin or other platinum-containing compounds or to nab-paclitaxel, Severe renal impairment (calculated GFR (CKD-EPI) < 60 mL/min/1.73 m2), myelosuppression (platelet count < 100.000/μl, hemoglobin < 9g/dl, neutrophil granulocytes < 1.500/ml), International Normalized Ratio (INR) > 2, severe hepatic (Serum total bilirubin > 1.5 mg/dl), respiratory or neurologic impairment (grade 3), severe myocardial insufficiency (NYHA class > 2), recent myocardial infarction, severe arrhythmias, Pregnancy or breastfeeding, women who can become pregnant must ensure effective contraception. Known or suspected non-compliance, inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant, Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Pressurized intraperitoneal aerosol chemotherapy (PIPAC) administration of Nab paclitaxel and cisplatin | Drug: Nab paclitaxel<br>* Dose escalation (7.5 mg/m2, 15 mg/m2, 25 mg/m2, 37.5 mg/m2, 52.5 mg/m2 and 70 mg/m2)<br>Drug: Cisplatin<br>* 10.5 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximal tolerated dose (MTD) of Nab paclitaxel (Abraxane®) administered IP by PIPAC in concomitance with cisplatin. | MTD is defined as the lowest dose level at which ≥33% of patients' experience dose limiting toxicity in accordance to CTCAE version 5.0 criteria. | From the time of treatment randomization through 30 days following cessation of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE) and serious adverse events (SAE) | AE and SAE with predefined toxicity criteria will be applied using CTCAE version 5.0 criteria, documented before and after each cycle of PIPAC treatment. Surgical complications will be assessed according to Clavien classification and comprehensive complication index (CCI) | D-1/D10 of each cycle | 
| The efficacy | It will be assessed by the objective histological regression and objective tumor response rate (OTR) according to the new regression system for peritoneal cancer (PRGS, peritoneal regression grade score system). The objective response rate (ORR), the clinical benefit rate (CBR) as defined by RECIST version 1.1 criteria and the relevance of radiological response assessed by CT enterography (CT-PCI score). | D0 of each cycle | 
| The QoL | QoL will be evaluated based on the EORTC questionnaire QLQ-C30 Version 3.0 and visual analogic scale for pain (VAS scale). | D-1/D10 of each cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, oeso-gastric cancer, epithelial ovarian cancer, primitive peritoneal mesothelioma