NCT01644994已完成1 期
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
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/1.73m
- •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
排除标准
- •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
研究组 & 干预措施
intracavitary cisplatin-fibrin
Experimental
single dose local intracavitary cisplatin-fibrin application after pleurectomy/decortication
干预措施: intracavitary cisplatin-fibrin (Combination Product)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety)
时间窗: 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
时间窗: 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
次要结局
- 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)
- pharmacokinetics cisplatin concentration in blood serum(baseline, and 0, 2, 6, 10, 24, 48, 120 h postoperative)
- pharmacokinetics cisplatin concentration in urine(baseline, collection of first 48h, day 14 postoperative)
- TUNEL assay(before and 90 min after cisplatin-fibrin application)
- PAI-1 and p21 (PAI-1 = Plasminogen Activator Inhibitor Typ 1, p21 = CDK-Inhibitor 1 = Cyclin Dependent Kinase Inhibitor 1))(before and 90 min after cisplatin-fibrin application)
研究者
研究点 (1)
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