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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
single dose, local intracavitary application of cisplatin-fibrin after pleurectomy/decortication
University Hospital Zurich, Division of Thoracic Surgery
Zurich, Canton of Zurich, Switzerland
Incidence of Treatment-Emergent Adverse Events (Safety)
(Serious) Adverse Events \& safety blood parameters (hematology and clinical chemistry)
Time frame: during 6 weeks after surgery with local cisplatin-fibrin application
Cisplatin concentration in the superficial chest wall tissue
local cisplatin concentration in the superficial chest wall biopsy measured by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
Time frame: 90 min after application
overall survival
time between date of treatment and time point of death or last follow-up, method of Kaplan and Meier
Time frame: up to 5 years (phase I), up to 2 years (phase II)
FFR (= Freedom From Recurrence)
time to tumor progression by CT or PET-CT/MRI, method of Kaplan and Meier
Time frame: 4, 16 weeks, then every 4 months up to 5 (phase I) / 2 years (phase II)
in-treatment-field FFR (= Freedom From Recurrence)
time to tumor progression by CT or PET-CT/MRI in the chest cavity where the investigational medicinal product was applied, method of Kaplan and Meier (PET-CT = positron emission computed tomography)
Time frame: up to 2 years (phase II)
Quality of Life SF-36 (= Short Form-36)
change from baseline in SF-36 quality of life questionnaire
Time frame: phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y
Quality of Life EORTC QLQ-C15/LC13 (QLQ = Quality of Life Questionnaire, C = Cancer, LC = Lung Cancer)
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change from baseline in EORTC Lung Cancer Questionnaire QLQ-C15/LC13
Time frame: phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y
pharmacokinetics cisplatin concentration in blood serum
cisplatin concentration in blood serum by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
Time frame: baseline, and 0, 2, 6, 10, 24, 48, 120 h postoperative
pharmacokinetics cisplatin concentration in urine
pharmacokinetics, cisplatin concentration in urine by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
Time frame: baseline, collection of first 48h, day 14 postoperative
TUNEL assay
markers for apoptosis in superficial chest wall tissue
Time frame: before and 90 min after cisplatin-fibrin application
PAI-1 and p21 (PAI-1 = Plasminogen Activator Inhibitor Typ 1, p21 = CDK-Inhibitor 1 = Cyclin Dependent Kinase Inhibitor 1))
markers for senescence in superficial chest wall tissue
Time frame: before and 90 min after cisplatin-fibrin application