intracavitary cisplatin-fibrin localized chemotherapy after p/d or epp for malignant pleural mesothelioma

Conditions: Malignant Pleural Mesothelioma

Summary: the aim is to introduce a new therapeutic method of intracavitary chemotherapy (cisplatin) combined with a fibrin carrier (vivostat®) after pleurectomy/decortication or extrapleural pneumonectomy in a phase i and ii study for malignant pleural mesothelioma patients by evaluation of the safety in a dose-escalating model (phase i), and confirmation of safety and efficacy in phase ii with the maximum tolerated dose in phase i.


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 (ecog = eastern cooperative oncology group) * resectable mpm (malignant pleural mesothelioma) histologically confirmed (phase i: stage ct1-ct4 cn0-cn3 cm0-cm1 / phase ii: stage ct1-ct3 cn0-cn1 cm0) (tnm tumor staging abbreviations: c = clinical; t = tumor, n = lymph nodes, m = metastases; numbers = quantity) * only phase ii: mediastinal staging (cytological or histological) * only phase ii: induction chemotherapy (3 or more cycles cisplatin or carboplatin (also in combination with other therapeutic agents) * patient qualifying for (extended) pleurectomy/decortication ((e)p/d) or extrapleural pneumonectomy (epp) for resection of mpm, which has to be assessed during a multidisciplinary tumor board including a thoracic surgeon * patient must have appropriate organ and bone marrow function as defined: hematologic function: hemoglobin ≥100 g/l, wbc (white blood cell count) ≥3.5 g/l, neutrophils ≥1.5 g/l, thrombocytes ≥100 g/l; liver function: total bilirubin and ldh (lactate dehydrogenase) ≤1.5 x uln (upper limit of normal); ast (aspartate aminotransferase), alt (alanine aminotransferase), ggt (gamma glutamyltransferase), and ap (alkaline phosphatase) ≤2.5 x uln; renal function: creatinine ≤130 μmol/l or, if greater, creatinine clearance ≥60 ml/min/1.73m2. * patient must have an appropriate blood coagulation for p/d or epp (quick-test \> 50%, inr (international normalized ratio) \<=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 ipsilateral pleurectomy * only phase ii: multimodality prognostic score (mmps) \> 2: 4 items with a maximum possible score of 4 if the patient presented all four conditions and 0 if none were present: tumor volume before induction chemotherapy \> 500 ml, non-epithelioid histotype in the diagnostic biopsy before induction chemotherapy, crp (c reactive protein) value \> 30 mg/l before induction chemotherapy, and progressive disease after induction chemotherapy according to recist criteria * patient with uncontrolled intercurrent illnesses that would limit the operative procedure of p/d / epp or compliance with study requirements * tinnitus impairment of more than severity grade i (slight) evaluated by the tinnitus questionnaire minitf12_ch (mini tinnitus fragebogen 12, ch = confoederatio helvetica (swiss version)), and/or restricted power of hearing until 4 khz (kilohertz) confirmed by audiometry, unless age-related presbyacusis in a normal range confirmed by an audiologist. * known alcohol and/or drug abuse at the time of screening * pregnant or lactating woman