Intracavitary Cisplatin-Fibrin Localized Chemotherapy After P/D or EPP for Malignant Pleural Mesothelioma
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: intracavitary cisplatin-fibrin single dose local intracavitary cisplatin-fibrin application after pleurectomy/decortication |
Combination Product: intracavitary cisplatin-fibrin
single dose, local intracavitary application of cisplatin-fibrin after pleurectomy/decortication
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse Events (Safety) [during 6 weeks after surgery with local cisplatin-fibrin application]
(Serious) Adverse Events & safety blood parameters (hematology and clinical chemistry)
- Cisplatin concentration in the superficial chest wall tissue [90 min after application]
local cisplatin concentration in the superficial chest wall biopsy measured by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
Secondary Outcome Measures
- overall survival [up to 5 years (phase I), up to 2 years (phase II)]
time between date of treatment and time point of death or last follow-up, method of Kaplan and Meier
- FFR (= Freedom From Recurrence) [4, 16 weeks, then every 4 months up to 5 (phase I) / 2 years (phase II)]
time to tumor progression by CT or PET-CT/MRI, method of Kaplan and Meier
- in-treatment-field FFR (= Freedom From Recurrence) [up to 2 years (phase II)]
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)
- Quality of Life SF-36 (= Short Form-36) [phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y]
change from baseline in SF-36 quality of life questionnaire
- Quality of Life EORTC QLQ-C15/LC13 (QLQ = Quality of Life Questionnaire, C = Cancer, LC = Lung Cancer) [phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y]
change from baseline in EORTC Lung Cancer Questionnaire QLQ-C15/LC13
- pharmacokinetics cisplatin concentration in blood serum [baseline, and 0, 2, 6, 10, 24, 48, 120 h postoperative]
cisplatin concentration in blood serum by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
- pharmacokinetics cisplatin concentration in urine [baseline, collection of first 48h, day 14 postoperative]
pharmacokinetics, cisplatin concentration in urine by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
- TUNEL assay [before and 90 min after cisplatin-fibrin application]
markers for apoptosis in superficial chest wall tissue
- PAI-1 and p21 (PAI-1 = Plasminogen Activator Inhibitor Typ 1, p21 = CDK-Inhibitor 1 = Cyclin Dependent Kinase Inhibitor 1)) [before and 90 min after cisplatin-fibrin application]
markers for senescence in superficial chest wall tissue
Other Outcome Measures
- pharmacokinetics cisplatin concentration in pleural effusion [Pleural effusion collection: 0-48 h postoperative]
cisplatin concentration in pleural effusion by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection
Eligibility Criteria
Criteria
Inclusion criteria:
-
Patient is able to understand and willing to sign a written informed consent document.
-
Male or female, age >=18 years
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ECOG performance status =<2 (ECOG = Eastern Cooperative Oncology Group)
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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)
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Only Phase II: Mediastinal staging (cytological or histological)
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Only Phase II: Induction chemotherapy (3 or more cycles cisplatin or carboplatin (also in combination with other therapeutic agents)
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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
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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.
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Patient must have an appropriate blood coagulation for P/D or EPP (Quick-test > 50%, INR (international normalized ratio) <=1.2)
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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).
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Heart and lung function allowing P/D under general anesthesia
Exclusion criteria:
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Known or suspected unwillingness of the patient to follow the rules of the protocol
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Patient who has not recovered from side effects from prior chemotherapy or radiotherapy.
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Any known hypersensitivity against cisplatin or other platinum containing substances or any other components used for the preparation of the drugs.
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Patient must not receive any other investigational agents 4 weeks before treatment and until the end of the observation period (2 months after treatment).
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Patient with prior ipsilateral pleurectomy
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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
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Patient with uncontrolled intercurrent illnesses that would limit the operative procedure of P/D / EPP or compliance with study requirements
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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.
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Known alcohol and/or drug abuse at the time of screening
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Pregnant or lactating woman
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Zurich, Division of Thoracic Surgery | Zurich | ZH | Switzerland | 8091 |
Sponsors and Collaborators
- University of Zurich
- Swiss National Science Foundation
- Swiss Accident Insurance Fund SUVA
Investigators
- Principal Investigator: Isabelle Opitz, Professor MD, University Hospital Zurich, Division of Thoracic Surgery
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INFLuenCe - Meso