Malignant Pleural Mesothelioma Clinical Trial
Official title:
Phase I Dose-Escalation /Phase II Monocentric Open Trial for Evaluation of Safety and Efficacy of Intracavitary Cisplatin-Fibrin Localized Chemotherapy After Pleurectomy/Decortication or Extrapleural Pneumonectomy for the Treatment of Patients With Malignant Pleural Mesothelioma
Verified date | September 2021 |
Source | University of Zurich |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 47 |
Est. completion date | August 2021 |
Est. primary completion date | December 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Switzerland | University Hospital Zurich, Division of Thoracic Surgery | Zurich | ZH |
Lead Sponsor | Collaborator |
---|---|
University of Zurich | Swiss Accident Insurance Fund SUVA, Swiss National Science Foundation |
Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | pharmacokinetics cisplatin concentration in pleural effusion | cisplatin concentration in pleural effusion by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection | Pleural effusion collection: 0-48 h postoperative | |
Primary | Incidence of Treatment-Emergent Adverse Events (Safety) | (Serious) Adverse Events & safety blood parameters (hematology and clinical chemistry) | during 6 weeks after surgery with local cisplatin-fibrin application | |
Primary | 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 | 90 min after application | |
Secondary | overall survival | time between date of treatment and time point of death or last follow-up, method of Kaplan and Meier | up to 5 years (phase I), up to 2 years (phase II) | |
Secondary | FFR (= Freedom From Recurrence) | time to tumor progression by CT or PET-CT/MRI, method of Kaplan and Meier | 4, 16 weeks, then every 4 months up to 5 (phase I) / 2 years (phase II) | |
Secondary | 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) | up to 2 years (phase II) | |
Secondary | Quality of Life SF-36 (= Short Form-36) | change from baseline in SF-36 quality of life questionnaire | phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y | |
Secondary | Quality of Life EORTC QLQ-C15/LC13 (QLQ = Quality of Life Questionnaire, C = Cancer, LC = Lung Cancer) | change from baseline in EORTC Lung Cancer Questionnaire QLQ-C15/LC13 | phase I: 0, 4, 8, 16 weeks and every 4w up to 5y; phase II: 0, 6, 16w and every 4w up to 2y | |
Secondary | pharmacokinetics cisplatin concentration in blood serum | cisplatin concentration in blood serum by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection | baseline, and 0, 2, 6, 10, 24, 48, 120 h postoperative | |
Secondary | pharmacokinetics cisplatin concentration in urine | pharmacokinetics, cisplatin concentration in urine by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection | baseline, collection of first 48h, day 14 postoperative | |
Secondary | TUNEL assay | markers for apoptosis in superficial chest wall tissue | before and 90 min after cisplatin-fibrin application | |
Secondary | 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 | before and 90 min after cisplatin-fibrin application |
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