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

NCT01644994 | Completed Phase 1

• 1 other identifier: INFLuenCe - Meso
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Pleural Mesothelioma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (9)

• overall survival

  up to 5 years (phase I), up to 2 years (phase II)

• FFR (= Freedom From Recurrence)

  4, 16 weeks, then every 4 months up to 5 (phase I) / 2 years (phase II)

• in-treatment-field FFR (= Freedom From Recurrence)

  up to 2 years (phase II)

• 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

• 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

Other Outcomes (1)

• pharmacokinetics cisplatin concentration in pleural effusion

  Pleural effusion collection: 0-48 h postoperative

Study Arms (1)

intracavitary cisplatin-fibrin

EXPERIMENTAL

single dose local intracavitary cisplatin-fibrin application after pleurectomy/decortication

Combination Product: intracavitary cisplatin-fibrin

Interventions

intracavitary cisplatin-fibrin COMBINATION_PRODUCT

single dose, local intracavitary application of cisplatin-fibrin after pleurectomy/decortication

intracavitary cisplatin-fibrin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• University of Zurich: lead
• Swiss National Science Foundation: collaborator
• Swiss Accident Insurance Fund SUVA: collaborator

Study Sites (1)

University Hospital Zurich, Division of Thoracic Surgery

Zurich, Canton of Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Isabelle Opitz, Professor MD

  University Hospital Zurich, Division of Thoracic Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open Label, single dose local intracavitary application of Cisplatin bound to Fibrin after surgery (removal of Tumor)

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 19, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2019
• Study Completion: August 1, 2021
• Last Updated: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)