Implementation and Evaluation of Pressurized Intrathoracic Aerosol Chemotherapy (PITAC) for the Treatment of Patients With Malignant Pleural Effusion. A Danish Phase I Study (OPC5 Study)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Medical adverse events
研究概览
简要总结
This study will monitor and evaluate patient and personnel safety and toxicity during the implementation and evaluation of Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) directed treatment. Furthermore, this study will focus on Quality of Life questionnaires, LENT score, and evaluate pain and breathlessness using af visual analogue scales (VAS).
详细描述
This is a safety and feasibility study of repeated (minimum two procedures) PITAC directed treatments, and the primary outcome is the number of patients with medical adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) and/or surgical complications according to the Clavien-Dindo classification. This study will include consecutive MPE patients until 20 patients have completed at least two PITAC´s. The PITAC directed treatment will be performed in 4 week intervals. Bedside ultrasound, VAS-pain and VAS-breathlessness, and Quality of Life questionnaires will be performed at baseline, one month follow-up and three months follow-up.
Patients with MPE who are eligible for surgery are identified during the multidisciplinary tumor (MDT) conference at the Department of Surgery, Odense University Hospital (OUH), and included based on predefined in- and exclusion criteria. Patients with MPE from non-colorectal or -appendix cancer will be treated with a combination of cisplatin and doxorubicin. Patients with MPE from colorectal or appendix cancer will be treated with oxaliplatin.
In brief, The PITAC procedure is the application of aerosolized chemotherapy into the pleural cavity using thoracoscopy. PITAC is performed in the prone or lateral position. A double lumen endotracheal tube is used to allow exclusion of the ipsilateral lung, but this is not (always) necessary with the patient in the prone position. The first trocar is placed guided by ultrasound, and after safe positioning a second trocar can be inserted guided by video thoracoscopy. The chemotherapy is applied to the pleural cavity through a nebulizer inserted through one of the trocars and linked to a high-pressure injector. After five minutes the chemotherapy has been delivered to the pleural cavity, and after an additional 30 minutes of simple diffusion, the intrathoracic air saturated with chemotherapy is evacuated through a series of filters.
The patients are monitored for a minimum of one day and will after each PITAC directed treatment be screened for adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 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
- •Symptomatic MPE visible with bedside ultrasound
- •Histologically or cytologically verified malignancy
- •Status CT-scan not older than four weeks
- •MPE requiring at least one drainage procedure
- •Drained ≥ 14 days before the first PITAC directed treatment
- •Bidirectional systemic chemotherapy or immunotherapy ≥ 14 days before the first PITAC directed treatment or no simultaneous systemic chemotherapy or immunotherapy
- •ECOG Performance status 0-2
- •Life expectancy ≥ 3 months
- •Age ≥ 18 years
- •Danish-speaking and reading patients
- •Written informed consent according to the local Ethics Committee requirements
排除标准
- •A history of allergic reaction to cisplatin or other platinum containing compounds or doxorubicin
- •Renal impairment, defined as GFR < 40 ml/min (Cockcroft-Gault Equation)
- •Myocardial insufficiency, defined as NYHA class > 2
- •Impaired liver function defined as bilirubin ≥1.5
- •Fertility, pregnancy and lactation: Female subjects will be considered of non-reproductive potential if they are either a, b or c:
- •postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- •have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening.
- •have a congenital or acquired condition that prevents childbearing. Previous intrathoracic chemotherapy, intrathoracic antibody treatment or chemical pleurodesis
- •Any other condition or therapy, which in the investigator´s opinion may pose a risk to the patient or interfere with the study objects
研究组 & 干预措施
PITAC
Malignant Pleural Effusion (MPE) from colorectal or appendix cancer will be treated with Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) using oxaliplatin 92 mg/m2 in 150 ml dextrose. MPE from non-colorectal or -appendix cancer will be treated with PITAC using cisplatin 10.5 mg/m2 in 150 ml saline and 2.1 mg/m2 in 50 ml saline.
PITAC is performed with a intrapleural pressure of 12 mmHg and the aerosolised chemotherapy will be nebulized at a maximum pressure of 300 PSI and a flow-rate of 0.5-1.8 ml/min. The PITAC directed treatment will be planned with 4 week intervals and patients may receive bi-directional systemic chemotherapy simultaneously.
干预措施: PITAC (Drug)
结局指标
主要结局
Medical adverse events
时间窗: 30 days from PITAC directed treatment
Number of patients with medical adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 defined as CTCAE ≥ 4 within 30 days after the procedure.
Surgical complications
时间窗: 30 days from PITAC directed treatment
Number of patients with surgical complications according to the Clavien-Dindo classification defined as Clavien-Dindo ≥ 3b within 30 days after the procedure.
次要结局
- Length of Stay (LOS)(12 months)
- Extent of visible pleural metastasis(12 months)
- LENT score(12 months)
- Lung function evaluation by FEV1(12 months)
- Number of patients completing three PITAC treatments(12 months)
- Pathology on pleural metastasis biopsies(12 months)
- Pain assessment(12 months)
- Survival(12 months)
- Cytology on malignant pleural effusion fluid(12 months)
- Personnel safety (biological)(12 months)
- Lung function evaluation by SAT(12 months)
- Personnel safety (environmental)(12 months)
- Change in MPE volume(12 months)
- Long term complications(12 months)
- Breathlessness(12 months)
- Quality of Life questionnaires(12 months)