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

This study is currently recruiting participants.
Verified August 2017 by University of Zurich
Sponsor:
ClinicalTrials.gov Identifier:
NCT01644994
First Posted: July 19, 2012
Last Update Posted: August 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Swiss National Science Foundation
Swiss Accident Insurance Fund SUVA
Information provided by (Responsible Party):
University of Zurich
  Purpose
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 Intervention Phase
Malignant Pleural Mesothelioma Combination Product: intracavitary cisplatin-fibrin Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Open Label, single dose local intracavitary application of Cisplatin bound to Fibrin after surgery (removal of Tumor)
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ 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 SF-36 quality of life questionnaire

  • Quality of Life EORTC QLQ-C15/LC13 (QLQ = Quality of Life Questionnaire, C = Cancer, LC = Lung Cancer) [ 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

  • pharmacokinetics cisplatin concentration in blood serum [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)) [ Time Frame: 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 [ Time Frame: Pleural effusion collection: 0-48 h postoperative ]
    cisplatin concentration in pleural effusion by inductively coupled plasma sector field mass spectrometric (ICP-MS) detection


Estimated Enrollment: 54
Study Start Date: November 2012
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01644994


Contacts
Contact: Isabelle Opitz, Professor MD +41 (0)44 255 11 11 isabelle.schmitt-opitz@usz.ch
Contact: Cordelia Bommeli, Study Coord. cordelia.bommeli@usz.ch

Locations
Switzerland
University Hospital Zurich, Division of Thoracic Surgery Recruiting
Zurich, ZH, Switzerland, 8091
Contact: Isabelle Opitz, Prof MD    +41 44 255 11 11    isabelle.schmitt-opitz@usz.ch   
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
  More Information

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01644994     History of Changes
Other Study ID Numbers: INFLuenCe - Meso
First Submitted: July 17, 2012
First Posted: July 19, 2012
Last Update Posted: August 24, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Cisplatin
Antineoplastic Agents