Intraperitoneal Paclitaxel for Patients With Primary Malignant Peritoneal Mesothelioma (INTERACT MESO)

The maximum tolerable dose (MTD) [ Time Frame: After two completed cycles of therapy (each cycle is 1 week) ]
The primary endpoint of the study is to determine the maximum tolerable dose (MTD) of intraperitoneal (IP) paclitaxel monotherapy, for patients with malignant peritoneal mesothelioma (MPM) who are not eligible to undergo CRS-HIPEC.

Toxicity assessment [ Time Frame: After two completed cycles of therapy (each cycle is 1 week) ]
Safety determined by toxicity assessment according to CTCAE version 5.0
Feasibility determined by the number of cycles given [ Time Frame: After eight completed cycles of therapy (each cycle is 1 week) ]
The treatment will be considered feasible if at least 50% of patients are able to finish 75% (i.e. 6) of total planned cycles (i.e. 8)
Area Under the Curve (AUC) [ Time Frame: At cycle 1 and 4 (each cylce is 1 week) ]
The 24-hour AUC will be calculated for systemic and intraperitoneal paclitaxel by obtaining blood and intraperitoneal fluid samples during the first and fourth treatment cycle, at time points prior to infusion, at the end of peritoneal infusion as well as every hour up to patients discharge.
Maximum concentration (Cmax) [ Time Frame: At cycle 1 and 4 (each cylce is 1 week) ]
The Cmax will be calculated by obtaining blood and intraperitoneal fluid samples during the first and fourth treatment cycle, at time points prior to infusion, at the end of peritoneal infusion as well as every hour up to patients discharge.
Elimination half life (t1/2) [ Time Frame: At cycle 1 and 4 (each cylce is 1 week) ]
The t1/2 will be calculated by obtaining blood and intraperitoneal fluid samples during the first and fourth treatment cycle, at time points prior to infusion, at the end of peritoneal infusion as well as every hour up to patients discharge.

Histological confirmed diagnosis of malignant peritoneal mesothelioma
Patients that are not eligible (or willing) to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC)
Age ≥ 18 years old
Written informed consent according to the ICH-GCP and national/local regulations
Patients must be ambulatory (WHO-ECOG performance status 0 or 1)
Ability to return to the Erasmus MC for adequate follow-up as required by this protocol
Patients must have normal organ function and adequate bone marrow reserve as assessed by the following laboratory requirements; absolute neutrophil count >1.5 * 10^9/l, platelet count >100*10^9/l and Hemoglobin >6.0mmol /l. Patients must have a Bilirubin < 1½ x upper limit of normal (ULN), Serum AST and ALT < 2.5 x ULN

Extra-abdominal disease/metastatic disease established by preoperative CT-scan of thorax-abdomen and/or PET-scan. Imaging not older than two months at time of surgery
Medical or psychological impediment to probable compliance with the protocol
Serious concomitant disease or active infections
History of auto-immune disease or organ allografts, or with active or chronic infection, including HIV and viral hepatitis
Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for participation in this study
Pregnant or lactating women; for all women of child-bearing potential a negative urine pregnancy test will be required as well as the willingness to use adequate contraception during the study until 4 weeks after finishing treatment
Absence of assurance of compliance with the protocol
An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up

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