Intracavitary Cisplatin-Fibrin Localized Chemotherapy After P/D or EPP for Malignant Pleural Mesothelioma

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 54
• Participant gender: Both

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Zurich
• Collaborators: Swiss Accident Insurance Fund SUVA; Swiss National Science Foundation
• Treatments: Cisplatin
• Last Updated: 2016-05-10

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

• 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

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 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