Intracavitary Cisplatin-Fibrin Localized Chemotherapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma

number of participants with adverse events [ Time Frame: during 4 weeks after surgery with local cisplatin-fibrin application ] [ Designated as safety issue: Yes ]
local cisplatin concentration in the superficial chest wall tissue (only Phase I) by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection [ Time Frame: 90 min after application ] [ Designated as safety issue: Yes ]
safety blood parameters (hematology and clinical chemistry) [ Time Frame: baseline and 1, 2, 3, 4, 5, 7, 10, 14 days postoperatively ] [ Designated as safety issue: Yes ]

overall survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
time to tumor progression by CT or PET-CT/MRI [ Time Frame: 4, 16 weeks, then every 4 months up to 5 years ] [ Designated as safety issue: No ]
change from baseline in SF-36 quality of life questionnaire [ Time Frame: 0, 4, 8 weeks ] [ Designated as safety issue: No ]
change from baseline in EORTC Lung Cancer Questionnaire QLQ-C15/LC13 [ Time Frame: 0, 4, 8 weeks ] [ Designated as safety issue: No ]
cisplatin concentration in blood serum by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection [ Time Frame: baseline before treatment with cisplatin-fibrin as well as at 0, 2, 6, 10, 24, 48, and 120 h postoperative ] [ Designated as safety issue: No ]; pharmacokinetics
cisplatin concentration in urine by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection [ Time Frame: collection of first 48h, day 14 postoperative ] [ Designated as safety issue: No ]; pharmacokinetics
TUNEL assay (markers for apoptosis in superficial chest wall tissue) [ Time Frame: before and 90 min after cisplatin-fibrin application ] [ Designated as safety issue: No ]
PAI-1 and p21 markers for senescence in superficial chest wall tissue [ Time Frame: before and 90 min after cisplatin-fibrin application ] [ Designated as safety issue: No ]

Eligibility Criteria

Inclusion criteria:

Patient is able to understand and willing to sign a written informed consent document.
Male or female, age >=18 years
ECOG performance status =2
MPM histologically confirmed (stage cT1-cT4 cN0-cN3 cM0-cM1)
Patient qualifying for pleurectomy/decortication (P/D) for resection of MPM, which has to be assessed during a multidisciplinary tumor board including a thoracic surgeon
Patient must have normal organ and bone marrow function as defined: normal hematologic function (hemoglobin >=100 g/L, WBC >=3.5 x G/L, neutrophils >=1.5 x G/L, thrombocytes >=100 x G/L), total bilirubin and liver function tests within normal institutional limits, creatinine within normal institutional limits or creatinine clearance >=60 ml/min/1.73m2 for patients with creatinine concentrations above institutional normal limits.
Patient must have an appropriate blood coagulation for P/D (Quick-test > 50%, aPTT within normal institutional limits, INR <=1.2)
The patient agrees to use an efficient contraceptive treatment up to 3 months after cisplatin application if required (pre-menopausal women and men in a sexually mature age).
Heart and lung function allowing P/D under general anesthesia

Exclusion criteria:

Known or suspected unwillingness of the patient to follow the rules of the protocol
Patient who has not recovered from side effects from prior chemotherapy or radiotherapy.
Any known hypersensitivity against cisplatin or other platinum containing substances or any other components used for the preparation of the drugs
Patient must not receive any other investigational agents 4 weeks before treatment and until the end of the observation period (2 months after treatment).
Patient with prior pleurectomy
Patient with uncontrolled intercurrent illnesses including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit the operative procedure of P/D or compliance with study requirements
Tinnitus and/or restricted power of hearing (especially in the upper frequency range) confirmed by audiometry
Known alcohol and/or drug abuse at the time of screening
Pregnant or lactating woman