INFLuenCe-Meso: Phase I/Phase II Study for the Evaluation of the Safety and Efficacy of Intracavitary Chemotherapy with Cisplatin-Fibrin after Pleurectomy/Decortication or Extrapleural Pneumonectomy for Patients with Malignant Pleural Mesothelioma. Original title: Phase I Dose-Escalation and Phase II Monocentric Open Trial for the Evaluation of the Safety and Efficacy of Intracavitary Cisplatin-Fibrin Localized Chemotherapy after Pleurectomy/Decortication or Extrapleural Pneumonectomy for the Treatment of Patients with Malignant Pleural Mesothelioma (INFLuenCe-Meso)
Zusammenfassung der Studie
Study to assess the safety and efficacy of localized chemotherapy with cisplatin-fibrin in the thoracic cavity after surgery for malignant pleural mesothelioma - a malignant tumor of the pleura. Phase I: Dose-escalation study (completed). Phase II: open, non-randomized interventional study on safety and efficacy (recruitment ongoing (as of May 2016)) Malignant pleural mesothelioma (MPM) remains an incurable tumor disease, with a poor prognosis and limited life expectancy even with multimodal therapy. Local tumor control remains one of the greatest challenges due to high recurrence rates. Local intracavitary chemotherapy after surgical removal of the tumor may improve local tumor control. In preclinical trials (small and large animal models, tumor and pharmacokinetic models), we achieved promising results with tumor removal plus intracavitary chemotherapy, where cisplatin was bound to a fibrin carrier. The local cisplatin concentration in the tissue could be increased while the systemic platinum concentration was significantly reduced, thereby also decreasing the rate of side effects. Cisplatin-fibrin was compared with local intracavitary chemotherapy with cisplatin as a solution, which is already in clinical use. The results indicate that local intracavitary chemotherapy with cisplatin-fibrin after cytoreductive surgery offers the same efficacy with an improved therapeutic index.
(BASEC)
Untersuchte Intervention
The treatment with cisplatin-fibrin is performed once after surgical removal of the tumor under general anesthesia. The operation, the preparatory examinations, and the postoperative care proceed in the same manner as for patients in whom the study drug is not used. Following the treatment, tissue samples are taken from the thoracic cavity 90 minutes after the treatment (still under general anesthesia) to determine the cisplatin content in the tissue. The pharmacokinetics of cisplatin are also studied in blood, urine, and thoracic drainage fluid.
The tolerability of the treatment is assessed with a quality of life questionnaire.
(BASEC)
Untersuchte Krankheit(en)
Malignant pleural mesothelioma - a malignant tumor of the pleura
(BASEC)
Patients (men and women ≥ 18 years, ECOG performance status ≤ 2) must be able to understand the meaning, content, and scope of the study and provide written consent. The diagnosis of resectable MPM must be confirmed by mediastinal lymph node staging (histologically or cytologically) (Phase I: stage cT1-cT4 cN0-cN3 cM0-cM1; Phase II: cT1-cT3 cN0-cN1 cM0). The patient must have undergone prior induction chemotherapy (3 cycles of cisplatin or carboplatin with pemetrexed). The patient's qualification for pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) must be confirmed by an interdisciplinary tumor board, with at least one thoracic surgeon present. Cardiac and pulmonary function must be adequate for P/D or EPP under general anesthesia. For inclusion in the study, patients must have adequate organ and bone marrow function and adequate blood coagulation. All study patients commit to effective contraception for up to 3 months after treatment if necessary. (BASEC)
Ausschlusskriterien
Patients will be excluded from the study if they have not recovered from adverse events of prior chemotherapy or radiotherapy, or if they have a known hypersensitivity to cisplatin or other platinum-containing substances as well as other components of cisplatin-fibrin. Patients must not take other study drugs 4 weeks prior to treatment and 2 months after treatment (observation period). Patients with prior ipsilateral pleurectomy are excluded. In Phase II: If the Multimodality Prognostic Score (MMPS) is greater than 2, the patient will be excluded. Patients with uncontrolled intercurrent diseases that would limit the surgical performance of a P/D or EPP or compliance with study conditions will not be included in the protocol. Patients with tinnitus greater than Grade I (mild) or hearing loss, especially in the range up to 4 kHz except for age-related presbycusis (after confirmation in an audiometric test in audiology, if anamnestically applicable), will be excluded. Patients who would not comply with the prescribed protocol or who have alcohol and drug abuse at the time of screening will not be included in the study. Pregnant or breastfeeding women are not allowed to participate. (BASEC)
Studienstandort
Zürich
(BASEC)
Sponsor
nicht verfügbar
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Schmitt-Opitz Isabelle
+41 44 255 11 11
isabelle.schmitt-opitz@clutterusz.ch(BASEC)
Allgemeine Auskünfte
University Hospital Zurich, Division of Thoracic Surgery
(ICTRP)
Wissenschaftliche Auskünfte
University Hospital Zurich, Division of Thoracic Surgery
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
nicht verfügbar
Datum der Bewilligung durch die Ethikkommission
11.08.2025
(BASEC)
ICTRP Studien-ID
NCT01644994 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
nicht verfügbar
Wissenschaftlicher Titel
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 (ICTRP)
Öffentlicher Titel
Intracavitary Cisplatin-Fibrin Localized Chemotherapy After P/D or EPP for Malignant Pleural Mesothelioma (ICTRP)
Untersuchte Krankheit(en)
Malignant Pleural Mesothelioma (ICTRP)
Untersuchte Intervention
Combination Product: intracavitary cisplatin-fibrin (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
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
(ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Cisplatin concentration in the superficial chest wall tissue;Incidence of Treatment-Emergent Adverse Events (Safety) (ICTRP)
PAI-1 and p21 (PAI-1 = Plasminogen Activator Inhibitor Typ 1, p21 = CDK-Inhibitor 1 = Cyclin Dependent Kinase Inhibitor 1));TUNEL assay;pharmacokinetics cisplatin concentration in urine;pharmacokinetics cisplatin concentration in blood serum;Quality of Life EORTC QLQ-C15/LC13 (QLQ = Quality of Life Questionnaire, C = Cancer, LC = Lung Cancer);Quality of Life SF-36 (= Short Form-36);in-treatment-field FFR (= Freedom From Recurrence);FFR (= Freedom From Recurrence);overall survival (ICTRP)
Registrierungsdatum
17.07.2012 (ICTRP)
Einschluss des ersten Teilnehmers
01.11.2012 (ICTRP)
Sekundäre Sponsoren
Swiss National Science Foundation;Swiss Accident Insurance Fund SUVA (ICTRP)
Weitere Kontakte
Isabelle Opitz, Professor MD, University Hospital Zurich, Division of Thoracic Surgery (ICTRP)
Sekundäre IDs
INFLuenCe - Meso (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
No (ICTRP)
Weitere Informationen zur Studie
https://clinicaltrials.gov/show/NCT01644994 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar