Clinical trial NCT06421610: OPC5: Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) in Patients With Malignant Pleural Effusion.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malignant Pleural Effusion
Pleural Neoplasms
Quality of Life
Chemotherapy Effect
Chemotherapeutic Toxicity
Pleural Carcinomatosis
Pleural Cavity Effusion
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2024-05-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cohort study
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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:

  1. 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.
  2. have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening.
  3. 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

Primary outcomes:
measure: Medical adverse events
timeFrame: 30 days from PITAC directed treatment
measure: Surgical complications
timeFrame: 30 days from PITAC directed treatment
Secondary outcomes:
measure: Number of patients completing three PITAC treatments
timeFrame: 12 months
measure: Extent of visible pleural metastasis
timeFrame: 12 months
measure: Pathology on pleural metastasis biopsies
timeFrame: 12 months
measure: Cytology on malignant pleural effusion fluid
timeFrame: 12 months
measure: LENT score
timeFrame: 12 months
measure: Length of Stay (LOS)
timeFrame: 12 months
measure: Personnel safety (environmental)
timeFrame: 12 months
measure: Personnel safety (biological)
timeFrame: 12 months
measure: Lung function evaluation by SAT
timeFrame: 12 months
measure: Breathlessness
timeFrame: 12 months
measure: Pain assessment
timeFrame: 12 months
measure: Quality of Life questionnaires
timeFrame: 12 months
measure: Change in MPE volume
timeFrame: 12 months
measure: Long term complications
timeFrame: 12 months
measure: Survival
timeFrame: 12 months
measure: Lung function evaluation by FEV1
timeFrame: 12 months
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense PIPAC Center, Department of Surgery, Odense University Hospital
Study officials:
References: