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.
|First Received Date||July 17, 2012|
|Last Changed Date||May 10, 2016|
|Start Date||November 2012|
|Anticipated Primary Completion Date||August 2020|
|Primary Outcome Measures||
number of participants with adverse events [Time Frame: during 4 weeks after surgery with local cisplatin-fibrin application]
local cisplatin concentration in the superficial chest wall tissue by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection [Time Frame: 90 min after application]
safety blood parameters (hematology and clinical chemistry) [Time Frame: baseline and 1, 2, 3, 4, 5, 7, 10, 14 days postoperatively]
|Secondary Outcome Measures||
overall survival [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 [Time Frame: 4, 16 weeks, then every 4 months up to 5 (phase I) / 2 years (phase II)]
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]
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]
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]
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 markers for senescence in superficial chest wall tissue [Time Frame: before and 90 min after cisplatin-fibrin application]
in-treatment-field FFR freedom from recurrence = time to tumor progression by CT or PET-CT/MRI in the chest cavitiy where the IMP was applied [Time Frame: up to 2 years (phase II)]
|Phase||Phase 1/Phase 2|
|Study Arms / Comparison Groups||1 / 0|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
Isabelle Opitz, Professor MD
Phone: +41 (0)44 255 11 11
- Patient is able to understand and willing to sign a written informed consent document.
- Male or female, age >=18 years
- ECOG performance status =<2
- Resectable MPM histologically confirmed (phase I: stage cT1-cT4 cN0-cN3 cM0-cM1 / phase II: stage cT1-cT3 cN0-cN1 cM0)
- Only Phase II: Mediastinal staging (cytological or histological)
- Only Phase II: Induction chemotherapy (3 cycles cisplatin or carboplatin combined with pemetrexed)
- Patient qualifying for pleurectomy/decortication (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 ≥3.5 x G/L, neutrophils ≥1.5 x G/L, thrombocytes ≥100 x G/L; liver function: total bilirubin and LDH ≤1.5 ULN; AST, ALT, GGT, and AP ≤2.5 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%, 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
- 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 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, and/or restricted power of hearing until 4 kHz 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
|Sponsor||University of Zurich|
|Verification Date||May 2016|